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Bai W, Wang Y, Ma J, Li G, Wang Y, Yang C, Zhang Q, Li Q, Zhang J, Zhang P. Histone deacetylase Hos1 promotes the homeostasis of Candida albicans cell wall and membrane and its specific inhibitor has an antifungal activity in vivo. Microbiol Res 2025; 296:128132. [PMID: 40112660 DOI: 10.1016/j.micres.2025.128132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Revised: 02/26/2025] [Accepted: 03/01/2025] [Indexed: 03/22/2025]
Abstract
The rise of drug-resistant Candida albicans (C. albicans) has led to an urgent need for new therapeutic strategies. Histone deacetylases (HDACs) inhibition has been shown to limit fungal virulence while enhancing the efficacy of antifungal drugs against Candida. However, HDACs are highly conserved from yeast to humans, which has hindered the application of these inhibitors in the antifungal therapy. The aim of this study is to identify a suitable antifungal target and develop specific inhibitors targeting C. albicans HDACs. Based on sequence alignments, the HDAC Hos1 in C. albicans was proposed as a target for further investigation. We evaluated the impact of Hos1 on C. albicans pathogenicity using a murine model of disseminated candidiasis. Results showed that Hos1 null mutant caused less damage to mouse tissues. Additionally, we demonstrated that the reduced virulence was due to inhibition of cell wall O-mannan biosynthesis and altered metabolic flexibility, leading to decreased adaptability of C. albicans. Increased sensitivity of C. albicans to antifungal drugs was attributed to abnormal accumulation of ergosterol in the cell membrane. Furthermore, we identified Hos1 inhibitors from the ZINC database using molecular docking. These inhibitors exhibited highly specific inhibition of the deacetylation activity of C. albicans Hos1. Importantly, the inhibitors not only reduced colonization and invasion by C. albicans in vivo but also synergized with polyene drugs to combat C. albicans by causing abnormal accumulation of ergosterol. Our findings provide detailed insights into antifungal targets and a useful foundation for the discovery of antifungal drugs specifically targeting Candida.
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Affiliation(s)
- Wenhui Bai
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Institute of Pharmaceutical Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Yanmei Wang
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Institute of Pharmaceutical Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Jia Ma
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi' an, Shaanxi 710061, China
| | - Guanglin Li
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Institute of Pharmaceutical Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Yuchen Wang
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Zonglian College, Xi'an Jiaotong University, Xi' an, Shaanxi 710061, China
| | - Chen Yang
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Institute of Pharmaceutical Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Qiyue Zhang
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Institute of Pharmaceutical Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Qingqing Li
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Institute of Pharmaceutical Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Jiye Zhang
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Institute of Pharmaceutical Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Peipei Zhang
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Institute of Pharmaceutical Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
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2
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da Silva Gebara R, da Silva MS, Calixto SD, Simão TLBV, Zeraik AE, Lassounskaia E, Muzitano MF, Petretski JH, Gomes VM, de Oliveira Carvalho A. Antifungal, Antimycobacterial, Protease and α‒Amylase Inhibitory Activities of a Novel Serine Bifunctional Protease Inhibitor from Adenanthera pavonina L. Seeds. Probiotics Antimicrob Proteins 2025; 17:1320-1342. [PMID: 38117407 DOI: 10.1007/s12602-023-10194-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/27/2023] [Indexed: 12/21/2023]
Abstract
Antifungal resistance poses a significant challenge to disease management, necessitating the development of novel drugs. Antimicrobial peptides offer potential solutions. This study focused on extraction and characterization of peptides from Adenanthera pavonina seeds with activity against Candida species, Mycobacterium tuberculosis, proteases, and α-amylases. Peptides were extracted in phosphate buffer and heated at 90°C for 10 min to create a peptide rich heated fraction (PRHF). After confirming antimicrobial activity and the presence of peptides, the PRHF underwent ion exchange chromatography, yielding retained and non-retained fractions. These fractions were evaluated for antimicrobial activity and cytotoxicity against murine macrophages. The least toxic and most active fraction underwent reversed-phase chromatography, resulting in ten fractions. These fractions were tested for peptides and antimicrobial activity. The most active fraction was rechromatographed on a reversed-phase column, resulting in two fractions that were assessed for antimicrobial activity. The most active fraction revealed a single band of approximately 6 kDa and was tested for inhibitory effects on proteases and α-amylases. Thermal stability experiments were conducted on the 6 kDa peptide at different temperatures followed by reassessment of antifungal activity and circular dichroism. The 6 kDa peptide inhibited yeasts, M. tuberculosis, human salivary and Tenebrio molitor larvae intestine α-amylases, and proteolytic activity from fungal extracts, and thus named ApPI. Remarkably, ApPI retained antifungal activity and conformation after heating and is primarily composed of α-helices. ApPI is a thermally stable serine protease/α-amylase inhibitor from A. pavonina seeds, offering promise as a foundational molecule for innovative therapeutic agents against fungal infections and tuberculosis.
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Affiliation(s)
- Rodrigo da Silva Gebara
- Laboratório de Fisiologia e Bioquímica de Microrganismos, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, 28013-602, RJ, Brazil
| | - Marciele Souza da Silva
- Laboratório de Fisiologia e Bioquímica de Microrganismos, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, 28013-602, RJ, Brazil
| | - Sanderson Dias Calixto
- Laboratório de Biologia do Reconhecer, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, 28013-602, RJ, Brazil
| | - Thatiana Lopes Biá Ventura Simão
- Laboratório de Biologia do Reconhecer, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, 28013-602, RJ, Brazil
| | - Ana Eliza Zeraik
- Laboratório de Química e Função de Proteinas e Peptídeos, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, 28013-602, RJ, Brazil
| | - Elena Lassounskaia
- Laboratório de Biologia do Reconhecer, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, 28013-602, RJ, Brazil
| | - Michelle Frazão Muzitano
- Laboratório de Produtos Bioativos, Universidade Federal do Rio de Janeiro, Macaé, 27933-378, RJ, Brazil
| | - Jorge Hudson Petretski
- Laboratório de Biologia do Reconhecer, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, 28013-602, RJ, Brazil
| | - Valdirene Moreira Gomes
- Laboratório de Fisiologia e Bioquímica de Microrganismos, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, 28013-602, RJ, Brazil
| | - André de Oliveira Carvalho
- Laboratório de Fisiologia e Bioquímica de Microrganismos, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, 28013-602, RJ, Brazil.
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3
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Lokhande SR, Adole VA, Rajesh R, Mali SN, Sadgir NV, Islam MS, Almutairi TM, Cruz JN, Patil MP, Jagdale BS. Synthesis, antifungal activity, molecular docking and DFT analysis of new (E)-4-(4-aryl)-2-(2-(1-(2,4-dimethoxyphenyl)ethylidene)hydrazineyl)thiazoles: An integrated experimental and theoretical study. J Mol Struct 2025; 1333:141761. [DOI: 10.1016/j.molstruc.2025.141761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/04/2025]
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Jaiswal N, Kumar A. Bioactive Phytophenolics of Vitex negundo Reveal Therapeutic Antifungal Potentials against Candida albicans. Chin J Integr Med 2025; 31:541-551. [PMID: 39551850 DOI: 10.1007/s11655-024-3913-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/22/2023] [Indexed: 11/19/2024]
Abstract
OBJECTIVE To map the potent antifungal properties of the medicinal plant Vitex negundo, in vitro and in silico studies were performed to decipher the pharmacokinetics and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties of their phytoconstituents. METHODS With the PASS (Prediction of Activity Spectra for Substances) prediction tool, many parameters of V. negundo phenolics were examined, including drug-likeness, bioavailability, antifungal activity, and anti-biofilm activity. Moreover, ADMET parameters were also determined. RESULTS Eighteen phenolic compounds from V. negundo with significant antifungal activity against Candida species (human fungal pathogens) were detected. The antioxidant activity, inhibition percentage, and minimum inhibitory concentration value of V. negundo phenolic extracts indicate it as an effective antifungal agent for the treatment of candidiasis caused by the fungal pathogen Candida albicans. Many phenolic compounds showed a significantly high efficiency against Candida's planktonic cells and biofilm condition. CONCLUSIONS The phenolics fraction of V. negundo has potent antifungal activities, however, some more pre-clinical studies are a matter of future research to further investigate V. negundo phenolic compound as a potential new antifungal arsenal.
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Affiliation(s)
- Neha Jaiswal
- Department of Biotechnology, National Institute of Technology, Raipur, CG, 492010, India
| | - Awanish Kumar
- Department of Biotechnology, National Institute of Technology, Raipur, CG, 492010, India.
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5
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Guimarães GG, Soares J, Resende AL, Gonçalves I, Blanco K, Bagnato V. Overcoming resistance of Candida albicans using photodynamic inactivation. Photochem Photobiol 2025. [PMID: 40371479 DOI: 10.1111/php.14108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2025] [Revised: 04/11/2025] [Accepted: 04/12/2025] [Indexed: 05/16/2025]
Abstract
The increasing resistance to conventional antifungal agents, such as Amphotericin B (AmB), has led to a growing demand for alternative therapeutic approaches for Candida albicans, an opportunistic fungal pathogen responsible for infections in immunocompromised patients. This study aimed to evaluate the effectiveness of photodynamic inactivation (PDI) in combination with AmB for controlling C. albicans growth, particularly in its yeast and hyphal forms, and to assess the impact of multiple PDI doses. C. albicans (ATCC 90028) was cultured in yeast and hyphal suspensions that were adjusted to 108 CFU/mL and treated with AmB at varying concentrations (0.065-1.04 μg/mL), with and without PDI. PDI was performed using the photosensitizer curcumin (2.5 μM), activated by a 450 nm LED light source at a fluence of 15 J/cm2. The effect of single and repeated PDI doses was evaluated in the fungal biomolecules, which were assessed using Fourier transform infrared (FTIR) spectroscopy. Optical density (OD) measurements quantified fungal growth reduction at 540 nm. The combination of AmB and PDI significantly reduced C. albicans growth, achieving a 75% reduction in the yeast form and an 87.5% reduction in the hyphal form. Two doses of PDI further enhanced antifungal efficacy, particularly against hyphae, which exhibited higher sensitivity to treatment. These findings suggest that PDI enhances the antifungal action of AmB, particularly in more resistant C. albicans forms such as hyphae and biofilms. The observed synergistic effect supports the potential use of PDI as an effective strategy to combat antifungal resistance in clinical applications.
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Affiliation(s)
- Gabriela Gomes Guimarães
- PPGBiotec, Federal University of São Carlos, Sao Carlos, Brazil
- São Carlos Institute of Physics, University of Sao Paulo, Sao Carlos, Brazil
| | - Jennifer Soares
- São Carlos Institute of Physics, University of Sao Paulo, Sao Carlos, Brazil
| | - Anna Luiza Resende
- São Carlos Institute of Physics, University of Sao Paulo, Sao Carlos, Brazil
| | - Isabella Gonçalves
- PPGBiotec, Federal University of São Carlos, Sao Carlos, Brazil
- São Carlos Institute of Physics, University of Sao Paulo, Sao Carlos, Brazil
| | - Kate Blanco
- São Carlos Institute of Physics, University of Sao Paulo, Sao Carlos, Brazil
| | - Vanderlei Bagnato
- PPGBiotec, Federal University of São Carlos, Sao Carlos, Brazil
- São Carlos Institute of Physics, University of Sao Paulo, Sao Carlos, Brazil
- Biomedical Engineering, Texas A&M University, College Station, Texas, USA
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6
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Silva DL, Peres NTA, Santos DA. Key fungal coinfections: epidemiology, mechanisms of pathogenesis, and beyond. mBio 2025; 16:e0056225. [PMID: 40172196 PMCID: PMC12077096 DOI: 10.1128/mbio.00562-25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/04/2025] Open
Abstract
Coinfection is defined as the occurrence of at least two genetically distinct infectious agents within the same host. Historically, fungal infections have been neglected, leading to an underestimation of their impact on public health systems. However, fungal coinfections have become increasingly prevalent, emerging as a significant global health concern. This review explores fungal coinfections commonly associated with HIV, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, Mycobacterium tuberculosis, and Pseudomonas species. These include candidiasis, aspergillosis, paracoccidioidomycosis, cryptococcosis, histoplasmosis, pneumocystosis, sporotrichosis, and mucormycosis. We discuss the key local and systemic mechanisms that contribute to the occurrence of these coinfections. HIV infects CD4+ cells, causing systemic immunosuppression, particularly impairing the adaptive immune response. The inflammatory response to SARS-CoV-2 infection disrupts both pulmonary and systemic homeostasis, rendering individuals more vulnerable to local and disseminated fungal coinfections. Severe influenza promotes fungal coinfections by triggering the production of pro-inflammatory cytokines, which damage the epithelial-endothelial barrier and impair the recognition and phagocytosis of fungal cells. Tuberculosis can replace normal lung parenchyma with collagen tissue, leading to alterations in lung architecture, compromising its function. Interaction between Pseudomonas and Aspergillus during coinfection involves the competition for iron availability and an adaptive response to its deprivation. Therefore, the specific interactions between each underlying disease and fungal coinfections are detailed in this review. In addition, we highlight the risk factors associated with coinfections, pathophysiology, epidemiology, and the challenges of early diagnosis. Recognizing the substantial worldwide public health burden posed by fungal coinfections is crucial to improve survival rates.
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Affiliation(s)
- Danielle L. Silva
- Microbiology Department, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, State of Minas Gerais, Brazil
| | - Nalu T. A. Peres
- Microbiology Department, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, State of Minas Gerais, Brazil
- Brazilian National Institute of Science and Technology in Human Pathogenic Fungi (INCT-FUNVIR), São Paulo, Brazil
| | - Daniel A. Santos
- Microbiology Department, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, State of Minas Gerais, Brazil
- Brazilian National Institute of Science and Technology in Human Pathogenic Fungi (INCT-FUNVIR), São Paulo, Brazil
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Jordão CC, Klein MI, Barbugli PA, Ferrisse TM, de Moraes JCG, Pavarina AC. The association of DNase I with antimicrobial photodynamic therapy affects Candida albicans gene expression and promotes immunomodulatory effects in mice with candidiasis. Photochem Photobiol Sci 2025:10.1007/s43630-025-00727-6. [PMID: 40325322 DOI: 10.1007/s43630-025-00727-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Accepted: 04/21/2025] [Indexed: 05/07/2025]
Abstract
This study evaluated Candida albicans gene expression and local inflammatory response from mice with oral candidiasis that were treated with DNase I plus antimicrobial photodynamic therapy (aPDT). DNase I was applied, followed by aPDT mediated by Photodithazine® and LED light, singly or combined for five consecutive days. A group was only inoculated with fluconazole-susceptible (CaS) or-resistant (CaR) C. albicans strains. Immediately and 7 days after treatments, C. albicans colonies recovered from mice tongues were used for gene expression evaluation. Tongues from mice killed 24 h and 7 days after treatments were used to evaluate the host's inflammatory cytokines using cytometric bead array. A reduction occurred in the gene expression related to adhesion to the host substrate, the biofilm extracellular matrix, and oxidative stress of CaS and CaR recovered from mice treated with DNAse I plus aPDT. Increased production of IL-6, TNF-α, and MCP-1 occurred in mice infected with CaS but not as much for those infected with CaR in the groups treated with DNase I plus aPDT and aPDT. DNase I plus aPDT decreased the expression of the fungal genes evaluated and increased local inflammatory response, which helped to fight the infection.
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Affiliation(s)
- Cláudia Carolina Jordão
- Laboratory of Applied Microbiology, Department of Dental Materials and Prosthodontics, São Paulo State University (UNESP), School of Dentistry, Araraquara, São Paulo, Brazil
| | - Marlise Inêz Klein
- Department of Oral Diagnosis, Piracicaba Dental School, State University of Campinas (UNICAMP), Piracicaba, São Paulo, Brazil
| | - Paula Aboud Barbugli
- Laboratory of Applied Microbiology, Department of Dental Materials and Prosthodontics, São Paulo State University (UNESP), School of Dentistry, Araraquara, São Paulo, Brazil
| | - Túlio Morandin Ferrisse
- Oral Radiology, Department of Diagnosis and Surgery, Araraquara Dental School, São Paulo State University (Unesp), Araraquara, Brazil
| | - Juliana Cerini Grassi de Moraes
- Laboratory of Applied Microbiology, Department of Dental Materials and Prosthodontics, São Paulo State University (UNESP), School of Dentistry, Araraquara, São Paulo, Brazil
| | - Ana Claudia Pavarina
- Laboratory of Applied Microbiology, Department of Dental Materials and Prosthodontics, São Paulo State University (UNESP), School of Dentistry, Araraquara, São Paulo, Brazil.
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Gupta SS, Kesarwani V, Shankar R, Sharma U. Chemoinformatics exploration of synthetically accessible N-heterocycles: uncovering new antifungal lead candidates. In Silico Pharmacol 2025; 13:74. [PMID: 40336776 PMCID: PMC12052619 DOI: 10.1007/s40203-025-00359-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Accepted: 04/07/2025] [Indexed: 05/09/2025] Open
Abstract
Fungal infections caused by Candida albicans pose a significant global health challenge due to their high morbidity, mortality, and the growing prevalence of drug resistance. The failure of existing antifungal agents against resistant strains underscores the urgent need for novel therapeutic alternatives. In response to this challenge, we have created an in-house library of biologically relevant nitrogenous heterocycles to screen against the resistant C. albicans dihydrofolate reductase (DHFR), with the aim of identifying potential antifungal leads. Using computational tools such as molecular docking and dynamics simulations, we identified two promising leads based on isoquinoline scaffold. The stability of these leads was further assessed using quantum chemical descriptor calculations. Screening results indicate that these isoquinoline-based compounds could serve as potential antifungal candidates, offering a foundation for the development of new therapies to combat resistant C. albicans infections. Further experimental studies, including animal model testing, are necessary to validate and confirm our findings. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s40203-025-00359-9.
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Affiliation(s)
- Shiv Shankar Gupta
- C-H Activation & Phytochemistry Lab, Chemical Technology Division, CSIR-IHBT, Palampur, HP 176061 India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002 India
| | - Veerbhan Kesarwani
- Studio of Computational Biology & Bioinformatics, The Himalayan Centre for High-Throughput Computational Biology (HiCHiCoB, A BIC Supported By DBT, Govt. of India), Biotechnology Division, CSIR-IHBT, Palampur, HP 176061 India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002 India
| | - Ravi Shankar
- Studio of Computational Biology & Bioinformatics, The Himalayan Centre for High-Throughput Computational Biology (HiCHiCoB, A BIC Supported By DBT, Govt. of India), Biotechnology Division, CSIR-IHBT, Palampur, HP 176061 India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002 India
| | - Upendra Sharma
- C-H Activation & Phytochemistry Lab, Chemical Technology Division, CSIR-IHBT, Palampur, HP 176061 India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002 India
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9
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Wang Z, Zhang Q, Zhang H, Lu Y. Roles of alcohol dehydrogenase 1 in the biological activities of Candida albicans. Crit Rev Microbiol 2025; 51:484-498. [PMID: 38916139 DOI: 10.1080/1040841x.2024.2371510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 04/21/2024] [Accepted: 06/04/2024] [Indexed: 06/26/2024]
Abstract
Candida albicans stands as the foremost prevalent human commensal pathogen and a significant contributor to nosocomial fungal infections. In the metabolism of C. albicans, alcohol dehydrogenase 1 (Adh1) is one of the important enzymes that converts acetaldehyde produced by pyruvate decarboxylation into ethanol at the end of glycolysis. Leveraging the foundational processes of alcoholic fermentation, Adh1 plays an active role in multiple biological phenomena, including biofilm formation, interactions between different species, the development of drug resistance, and the potential initiation of gastrointestinal cancer. Additionally, Adh1 within C. albicans has demonstrated associations with regulating the cell cycle, stress responses, and various intracellular states. Furthermore, Adh1 is extracellularly localized on the cell wall surface, where it plays roles in processes such as tissue invasion and host immune responses. Drawing from an analysis of ADH1 gene structure, expression patterns, and fundamental functions, this review elucidates the intricate connections between Adh1 and various biological processes within C. albicans, underscoring its potential implications for the prevention, diagnosis, and treatment of candidiasis.
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Affiliation(s)
- Ziqi Wang
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
| | - Qi Zhang
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
| | - Haoying Zhang
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
| | - Yuanyuan Lu
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
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10
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de Jong PRC, Wijffels MME, Rijnders BJA, Juffermans N. Lethal soft-tissue necrosis early after organ transplantation: a case report. Ann Med Surg (Lond) 2025; 87:2987-2991. [PMID: 40337413 PMCID: PMC12055108 DOI: 10.1097/ms9.0000000000003026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Accepted: 01/21/2025] [Indexed: 05/09/2025] Open
Abstract
Introduction and importance Necrotizing soft tissue infection (NSTI) is a rapidly spreading infection which affects subcutaneous tissue, extending to a muscular level. Early and aggressive surgical exploration is frequently necessary, especially in patients with significant comorbidities or advanced age. NSTIs are commonly caused by Streptococcus pyogenes or methicillin resistant Staphylococcus aureus, though monomicrobial infections with Candida species have been reported. Case presentation A 64-year-old developed an NSTI of the upper left leg following bilateral lung transplantation. The patient presented with atypical clinical and radiographical symptoms, leading to initial management with antimicrobial therapy. Cultures taken preoperatively and intraoperatively were positive for Candida albicans without the presence of other microorganisms. Surgical exploration revealed extensive necrosis of the upper left leg and groin, resulting in deep sepsis which ultimately led to the patient's death. Clinical discussion NSTI should be monitored with extra vigilance in immunocompromised or otherwise at risk patients, especially when exhibiting atypical symptoms or disease course. Extensive surgical exploration remains the cornerstone of adequate treatment. Conclusion NSTIs caused by monomicrobial infections with C. albicans are rare and typically progress rapidly. We report a case of monomicrobial NSTI in an immunocompromised patient following bilateral lung transplantation characterized by atypical presentation and course, with C. albicans as the main pathogen.
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Affiliation(s)
- Pieter R. C. de Jong
- Department of General Surgery, Erasmus Medical Center, Rotterdam, the Netherlands
| | | | - Bart J. A. Rijnders
- Department of Microbiology, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Nicole Juffermans
- Intensive Care Unit, Erasmus Medical Center, Rotterdam, the Netherlands
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11
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Wilson L, Nielsen K, Caspasso-Villanueva S, O'Brien T, Hefner LA, Slick P, Petty L, Dienna R, Castillo H, Chavez A. Characterization of virulence-related phenotypes of Candida parapsilosis and Rhodotorula mucilaginosa isolated from the International Space Station (ISS). LIFE SCIENCES IN SPACE RESEARCH 2025; 45:16-24. [PMID: 40280638 DOI: 10.1016/j.lssr.2025.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Revised: 01/09/2025] [Accepted: 01/15/2025] [Indexed: 04/29/2025]
Abstract
There is increased interest in characterizing and describing the effects of space stressors on human microflora. This study describes virulence-related phenotypes of two human yeast commensals, Rhodotorula mucilaginosa and Candida parapsilosis, isolated from the International Space Station (ISS). The strains were compared with ATCC control strains to provide insights into adaptation and phenotypic switching of fungal species in spacecraft environments. Strains were grown in media that induce filamentation and capsule production. Antimycotic susceptibility was determined after exposure of liquid cultures to fluconazole, amphotericin B, and caspofungin. Biofilm formation was quantified using the crystal violet assay, and autoinducer (AI) production was detected by activation of a reporter fluorescent gene present in biosensor bacterial strains. In vivo infection studies were conducted using a C. elegans killing model. Results indicated increased filamentation production patterns in ISS Candida parapsilosis and increased capsule production in ISS Rhodotorula. Additionally, there was increased resistance to antifungal activity, biofilm formation, long-chain autoinducer production, and heightened nematode virulence detected in the ISS isolates. These results suggest that space conditions might enhance adaptation and phenotypic plasticity in yeast, leading to increased virulence-related phenotypes.
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Affiliation(s)
- Lauren Wilson
- Department of Human Factors and Behavioral Neurobiology, College of Arts and Sciences, Embry-Riddle Aeronautical University, 1 Aerospace Blvd, Daytona Beach 32114, FL, USA
| | - Kaitlyn Nielsen
- Department of Human Factors and Behavioral Neurobiology, College of Arts and Sciences, Embry-Riddle Aeronautical University, 1 Aerospace Blvd, Daytona Beach 32114, FL, USA
| | - Stefani Caspasso-Villanueva
- Department of Human Factors and Behavioral Neurobiology, College of Arts and Sciences, Embry-Riddle Aeronautical University, 1 Aerospace Blvd, Daytona Beach 32114, FL, USA
| | - Takara O'Brien
- Department of Human Factors and Behavioral Neurobiology, College of Arts and Sciences, Embry-Riddle Aeronautical University, 1 Aerospace Blvd, Daytona Beach 32114, FL, USA
| | - Lily A Hefner
- Westminster College, 501 Westminster Avenue, Fulton, MO 665251, USA
| | - Paulina Slick
- Department of Integrative Biology, College of Arts and Sciences, University of South Florida, 4202 E Fowler Ave, Tampa, Florida 33620, USA
| | - Logan Petty
- Department of Human Factors and Behavioral Neurobiology, College of Arts and Sciences, Embry-Riddle Aeronautical University, 1 Aerospace Blvd, Daytona Beach 32114, FL, USA
| | - Riley Dienna
- Department of Human Factors and Behavioral Neurobiology, College of Arts and Sciences, Embry-Riddle Aeronautical University, 1 Aerospace Blvd, Daytona Beach 32114, FL, USA
| | - Hugo Castillo
- Department of Human Factors and Behavioral Neurobiology, College of Arts and Sciences, Embry-Riddle Aeronautical University, 1 Aerospace Blvd, Daytona Beach 32114, FL, USA
| | - Alba Chavez
- Department of Human Factors and Behavioral Neurobiology, College of Arts and Sciences, Embry-Riddle Aeronautical University, 1 Aerospace Blvd, Daytona Beach 32114, FL, USA.
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12
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Sang QY, Liao YH, Huang KX, Xie YR, Yao YH, Chen P, Liang XM. In vitro susceptibility profiles of invasive Candida bloodstream isolates to ten antifungal drugs in a southern area of China. J Med Microbiol 2025; 74:002011. [PMID: 40354110 PMCID: PMC12069814 DOI: 10.1099/jmm.0.002011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Accepted: 04/21/2025] [Indexed: 05/14/2025] Open
Abstract
Introduction. In recent years, with the increase of drug resistance of Candida, the incidence rate and mortality of candidemia have gradually increased, which has brought a huge economic and health burden to people.Gap Statement. The epidemiological characteristics and antifungal drug sensitivity patterns in different regions have varied.Aim. To analyse the distribution and antifungal susceptibility of Candida strains isolated from bloodstreams and provide a basis for the use of antifungal drugs for treatment.Methodology. A total of 115 strains of Candida were collected from the bloodstream, and 28 strains of colonized Candida albicans were collected from the upper respiratory tract. Candida species were identified using matrix-assisted laser desorption/ionization time-of-flight technology. Antifungal susceptibility was assessed using broth microdilution combined with redox methods.Results. There were eight types of Candida strains isolated from the bloodstream; C. albicans was the most common species (36.5%), followed by Candida parapsilosis (24.3%), Candida glabrata (17.4%) and Candida tropicalis (14.8%). There was no significant difference in the resistance of C. albicans to azole drugs between the bloodstream infection group and the upper respiratory tract colonization group, but there was a significant difference in the MIC values of micafungin and fluconazole, with P values of 0.017 and 0.003, respectively. Amphotericin B and echinocandins are the most susceptible drugs for all Candida species, but the MICs of echinocandins against C. parapsilosis are significantly higher than those of other Candida species. Candida (except for C. glabrata) is highly resistant to azoles, with C. parapsilosis showing resistance rates of 89.3% and 82.1% to itraconazole and posaconazole, respectively; the resistance rates of C. tropicalis are 100% and 94.1%, respectively.Conclusion. C. albicans remains the predominant pathogen responsible for candidemia. Although the resistance of Candida to antifungals is relatively stable, there are significant differences in the MICs of antifungal drugs against Candida, indicating the importance of strain identification in the treatment of candidemia. For empirical treatment, the use of echinocandin drugs is recommended.
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Affiliation(s)
- Qian-Yu Sang
- Department of Clinical Laboratory, Xiamen Hospital of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Xiamen 361000, PR China
| | - Yun-Hui Liao
- Department of Clinical Laboratory, Xiamen Hospital of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Xiamen 361000, PR China
| | - Kai-Xuan Huang
- Department of Clinical Laboratory, Xiamen Hospital of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Xiamen 361000, PR China
| | - Yin-Rong Xie
- Department of Clinical Laboratory, Xiamen Hospital of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Xiamen 361000, PR China
| | - Yi-Hui Yao
- Centre of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, PR China
| | - Ping Chen
- Department of Clinical Laboratory, Xiamen Hospital of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Xiamen 361000, PR China
- Clinical Laboratory Branch, Xiamen Association of Integrative Chinese and Western Medicine, Xiamen 361000, PR China
| | - Xian-Ming Liang
- Department of Clinical Laboratory, Xiamen Hospital of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Xiamen 361000, PR China
- Clinical Laboratory Branch, Xiamen Association of Integrative Chinese and Western Medicine, Xiamen 361000, PR China
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13
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Olender A, Bogut A, Dąbrowski W, Pietrzak DJ, Szukała M, Wójtowicz-Bobin M, Kubera D, Dróżdż A, Stepulak A, Gagoś M. Analysis of Antifungal Drug Resistance Among Candida Spp. and Other Pathogenic Yeasts Isolated from Patients in Eastern Poland: Diagnostic Problems. Infect Drug Resist 2025; 18:2187-2199. [PMID: 40321598 PMCID: PMC12049117 DOI: 10.2147/idr.s504516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 02/07/2025] [Indexed: 05/08/2025] Open
Abstract
Objective The profile of Candida species and their sensitivity to antifungal drugs isolated from patients in Eastern Poland were analyzed. Identification and drug resistance interpretation issues for clinically significant rare species were investigated. Methods A total of 197 yeast isolates were analyzed. Fungal identification was conducted using biochemical tests and MALDI-TOF. Minimum inhibitory concentrations (MICs) were determined for amphotericin B, fluconazole, itraconazole, voriconazole, isavuconazole, posaconazole, caspofungin, micafungin, and anidulafungin. Interpretation of results was based on the EUCAST, CLSI recommendations, and available literature. Results The following species were identified: Candida albicans (n=78), C. glabrata (Nakaseomyces glabrata) (n=30), C. dubliniensis (n=23), C. krusei (Pichia kudriavzevii) (n=13), C. parapsilosis (n=13), C. tropicalis (n=7), C. kefyr (Kluyveromyces marxianus) (n=6), C. lusitaniae (Clavispora lusitaniae) (n=6), C. lipolytica (Yarrowia lipolytica) (n=3), C. famata (Debaryomyces hansenii) (n=2), C. intermedia (n=2), C. guillermondii (Meyerozyma guilliermondii) (n=2), C. ciferrii (n=1), C. orthopsilosis (n=1), C. pelliculosa (Wickerhamomyces anomalus) (n=1), C. shehatae (n=1), C. fabianii (Cyberlindnera fabianii) (n=1), Cryptococcus humicola (Vanrija humicola) (n=4), and Saccharomyces cerevisiae (n=3). The highest percentage of resistant strains was reported for C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, and C. lusitaniae. Conclusion Among the studied isolates, rare Candida species were identified. Their identification in routine diagnostics can be challenging, necessitating the use of MALDI-TOF MS. The wide spectrum of isolated species may complicate the establishment of a targeted antifungal therapy due to the lack of reference MIC ranges for the interpretation of antibiograms. Gradient strips are an accurate, reproducible, and convenient method for MIC determination.
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Affiliation(s)
- Alina Olender
- Chair and Department of Medical Microbiology, Medical University of Lublin, Lublin, Poland
| | - Agnieszka Bogut
- Chair and Department of Medical Microbiology, Medical University of Lublin, Lublin, Poland
| | - Wojciech Dąbrowski
- First Department of Anaesthesiology and Intensive Therapy Medical University of Lublin, Lublin, Poland
| | - Daniel Jarosław Pietrzak
- First Department of Anaesthesiology and Intensive Therapy Medical University of Lublin, Lublin, Poland
| | - Magdalena Szukała
- First Department of Anaesthesiology and Intensive Therapy Medical University of Lublin, Lublin, Poland
| | | | - Dominika Kubera
- Faculty of Physics and Applied Computer Science, AGH University of Kraków, Kraków, Poland
| | - Agnieszka Dróżdż
- Faculty of Physics and Applied Computer Science, AGH University of Kraków, Kraków, Poland
| | - Andrzej Stepulak
- Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland
| | - Mariusz Gagoś
- Faculty of Physics and Applied Computer Science, AGH University of Kraków, Kraków, Poland
- Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland
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14
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Diez A, Arrieta-Aguirre I, Carrano G, Bregón-Villahoz M, Moragues MD, Fernandez-de-Larrinoa I. A synthetic peptide vaccine induces protective immune responses against Candida albicans infection in immunocompromised mice. Vaccine 2025; 53:127102. [PMID: 40194489 DOI: 10.1016/j.vaccine.2025.127102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 03/31/2025] [Accepted: 04/01/2025] [Indexed: 04/09/2025]
Abstract
Invasive fungal infections, such as those caused by Candida species, predominantly affects hospitalized and immunocompromised patients. Current mortality rates are expected to rise as drug-resistant fungal species increase and the pool of immunocompromised individuals grows. Today, antifungal treatments show limited effectiveness, underscoring the need for new safe and effective antifungal vaccines. This study investigates the efficacy of a protective immunization strategy with DC stimulated by a synthetic peptide, 3P-KLH, containing epitopes from three Candida albicans proteins (Als3, Hwp1 and Met6) against a model of invasive candidiasis raised in immunosuppressed mice. Immunization effectively stimulated both humoral and cellular immune responses, as indicated by high antibody titers to the synthetic fungal peptide, increased cytokine levels, reduced fungal burden in kidneys and improved survival outcomes following infection. Although the variability in fungal burden in the control group limited the statistical significance for fungal clearance data, immunized mice showed a 64-fold lower fungal burden in renal tissues compared to controls. Cytokine analysis revealed elevated levels of IL-2, IL-17, and IFN-γ, suggesting a strong activation of Th1 and Th17 responses, both essential for antifungal immunity. Survival data further supported the protective effect of the immunogenic agent: 62.5 % immunized mice survived the 21-day post-infection period compared to 100 % mortality in controls. The progressively lower fungal burden over time in surviving mice suggests a sustained immune response that continues to suppress fungal replication. These results suggest that the immunization with the synthetic peptide stimulates a strong immune response, involving both antibody production and cell-mediated immunity, making it a promising candidate for therapeutic strategies against invasive candidiasis. Future work should focus on optimizing this immunization approach, assessing long-term immunity, and evaluating its potential in other fungal infection models.
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Affiliation(s)
- Ander Diez
- Department of Immunology, Microbiology and Parasitology, University of the Basque Country UPV/EHU, Leioa, Spain.
| | | | - Giulia Carrano
- Department of Immunology, Microbiology and Parasitology, University of the Basque Country UPV/EHU, Leioa, Spain
| | - Marta Bregón-Villahoz
- Department of Immunology, Microbiology and Parasitology, University of the Basque Country UPV/EHU, Leioa, Spain
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15
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Kumar A, Yadav B, Roy A, Mishra P, Poluri KM, Gupta P. Biochemical insights into synergistic Candida biofilm disintegrating ability of p-cymene inclusion complex and miconazole. Eur J Pharmacol 2025; 993:177365. [PMID: 39938856 DOI: 10.1016/j.ejphar.2025.177365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 02/03/2025] [Accepted: 02/07/2025] [Indexed: 02/14/2025]
Abstract
Phytoactive molecules emerge as a plentiful reservoir of adjuvant and antifungal agents. The resolution of solubility and stability issues has been facilitated by developing molecular complexes or inclusion complexes of phytoactive molecules. Miconazole (MCZ) is a favoured azole with low off-target impact, however, its pharmacological efficacy requires a revamp to enhance its suitability as an antifungal drug. Hence, the present investigation delves into the mechanism of action of the p-cymene/β-cyclodextrin inclusion complex (IC) along with MCZ against Candida albicans and Candidaglabrata biofilms. The synergy between IC and MCZ has been estimated at a concentration of 6.25 μg/mL IC + 0.5 μg/mL MCZ with a FICI of 0.19. The prepared IC + MCZ displayed remarkable antifungal properties against planktonic and sessile growth of Candida species. IC + MCZ exhibited a notable 80% biofilm eradication potential against both species, corroborated by morphological analysis using FE-SEM. The results indicated that IC/IC + MCZ acts by disrupting the biochemical composition of the ECM, altering the surface properties of the cells, reducing ergosterol, enhancing membrane permeability, and inducing oxidative stress. In conclusion, the study highlighted the synergistic antibiofilm activity of p-cymene IC with miconazole against Candida species. In summary, IC + MCZ has been established as a potent antifouling agent against Candida species, warranting further exploration for potential formulation with additional investigations.
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Affiliation(s)
- Amit Kumar
- Department of Biotechnology, Graphic Era Deemed to Be University, Dehradun, 248001, Uttarakhand, India
| | - Bhawana Yadav
- Department of Biotechnology, Graphic Era Deemed to Be University, Dehradun, 248001, Uttarakhand, India
| | - Ankita Roy
- Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, 247667, Uttarakhand, India
| | - Purusottam Mishra
- Biotechnology Centre, Silesian University of Technology, 8 Krzywousty Street, Gliwice, 44-100, Poland
| | - Krishna Mohan Poluri
- Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, 247667, Uttarakhand, India; Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, 247667, Uttarakhand, India.
| | - Payal Gupta
- Department of Biotechnology, Graphic Era Deemed to Be University, Dehradun, 248001, Uttarakhand, India.
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16
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Dusza I, Jama D, Skaradziński G, Śliwka P, Janek T, Skaradzińska A. Bacteriophages Improve the Effectiveness of Rhamnolipids in Combating the Biofilm of Candida albicans. Molecules 2025; 30:1772. [PMID: 40333731 PMCID: PMC12029421 DOI: 10.3390/molecules30081772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Revised: 04/03/2025] [Accepted: 04/08/2025] [Indexed: 05/09/2025] Open
Abstract
Biofilms formed by Candida albicans pose therapeutic challenges due to their resistance to conventional antimicrobials, highlighting the need for more effective treatments. Rhamnolipids (RLs) are biosurfactants with diverse antimicrobial properties. Bacteriophages are viruses that target specific bacterial strains. Recent studies have shown that they may affect biofilm formation by fungi and yeasts. This study investigated the combined antimicrobial effects of RLs and bacteriophages against C. albicans biofilms, focusing on their anti-adhesive and inhibitory effects on biofilm development. RT-PCR assays were used to analyze gene modulation in C. albicans biofilm formation in response to RLs and bacteriophage treatments, while hyphae formation was examined using microscopy. The results showed that RLs-bacteriophage combinations significantly reduced biofilm formation compared to individual treatments. A combination of 200 mg/L RLs with bacteriophage BF9 led to a 94.8% reduction in biofilm formation. In a subsequent model, the same RL concentration with bacteriophage LO5/1f nearly eliminated biofilm formation (~96%). Gene expression analysis revealed downregulation of key biofilm-associated genes when Candida cells were treated with 200 mg/L RLs and four bacteriophages (BF17, LO5/1f, JG004, FD). These results show the potential of RL and bacteriophage combinations in combating C. albicans biofilms, presenting a promising therapeutic approach against resilient infections.
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Affiliation(s)
| | | | | | | | | | - Aneta Skaradzińska
- Department of Biotechnology and Food Microbiology, Faculty of Biotechnology and Food Science, Wrocław University of Environmental and Life Sciences, Chełmońskiego 37, 51-630 Wrocław, Poland
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17
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Frolov NA, Tyutin AA, Tyurina AN, Seferyan MA, Detusheva EV, Son E, Saverina EA, Vereshchagin AN. Expanding the Variety of Pyridinium-Based Bis-QACs with Antimicrobial Properties: Investigation into Linker Structure-Activity Correlation. ChemMedChem 2025; 20:e202400972. [PMID: 39821485 DOI: 10.1002/cmdc.202400972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 01/13/2025] [Accepted: 01/14/2025] [Indexed: 01/19/2025]
Abstract
For decades quaternary ammonium compounds (QACs) have served as main component of a top antiseptic and disinfectant compositions. Among them, bis-QACs are the most prominent and effective class of biocides. Although mono-QACs still dominate the antiseptic market, their activity against Gram-negative bacteria is largely inferior to bis-QACs. Moreover, the new wave of bacterial resistance during the COVID-19 pandemic is threatening the efficiency of popular antiseptics. Therefore, the requirement for novel biocides is urgent. Reported here is a unified and simple two-step synthesis to achieve novel biocide's architectures with aromatic linkers. Thus, a series of 14 bis-QACs have been prepared using an Ullman-type reaction following by N-alkylation. The most prominent compounds showed strong bioactivity against a panel of nineteen microbial pathogens, multi-resistant bacterial ESKAPEE strains, fungi and biofilms, including strains, which acquired resistance during COVID-19 in 2021. Moreover, significant improvements in antibiofilm action were observed, where bis-QACs 5 c and 6 a outperformed gold standard pyridinium antiseptic octenidine. These findings will serve as a good basis for further studies of bis-QACs architectures as highly effective biocides.
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Affiliation(s)
- Nikita A Frolov
- N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991, Moscow, Russia
| | - Alexander A Tyutin
- N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991, Moscow, Russia
- Mendeleev University of Chemical Technology of Russia, Departments of the Faculty of Natural Sciences and Department of Chemistry and Technology of Biomedical Drugs, Miusskaya square 9, 125047, Moscow, Russia
| | - Alexandra N Tyurina
- Mendeleev University of Chemical Technology of Russia, Departments of the Faculty of Natural Sciences and Department of Chemistry and Technology of Biomedical Drugs, Miusskaya square 9, 125047, Moscow, Russia
| | - Mary A Seferyan
- N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991, Moscow, Russia
| | - Elena V Detusheva
- N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991, Moscow, Russia
- Federal Budget Institution of Science «State research center for applied microbiology and biotechnology», 142279, Obolensk, Serpukhov, Moscow Region, Russia
| | - Elizabeth Son
- Federal Budget Institution of Science «State research center for applied microbiology and biotechnology», 142279, Obolensk, Serpukhov, Moscow Region, Russia
| | - Evgeniya A Saverina
- N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991, Moscow, Russia
- Federal State Budgetary Educational Institution of Higher Education, Tula State University, Prospekt Lenina 92, 300012, Tula, Russia
| | - Anatoly N Vereshchagin
- N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991, Moscow, Russia
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18
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Faustino M, Ferreira CMH, Pereira AM, Carvalho AP. Candida albicans: the current status regarding vaginal infections. Appl Microbiol Biotechnol 2025; 109:91. [PMID: 40210803 PMCID: PMC11985607 DOI: 10.1007/s00253-025-13478-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 04/01/2025] [Accepted: 04/02/2025] [Indexed: 04/12/2025]
Abstract
Vaginal infections caused by Candida albicans are a significant global health concern due to their recurrence and negative impact on quality of life. This review examines the pathogenesis of C. albicans infections, emphasizing critical virulence factors such as biofilm formation, adherence, and phenotypic switching. Risk factors include immune system suppression, antibiotic use, and hormonal changes, all of which can lead to fungal overgrowth and infection. Current prevention and/or treatment strategies primarily rely on antifungal therapies, personal hygiene practices, and probiotics. However, challenges like antifungal resistance, recurrence, and limited treatment efficacy highlight the need for innovative approaches. Therefore, emerging methods such as novel antifungal agents, vaccines, and nanotechnology-based delivery systems offer promising advancements to improve infection control. Additionally, the immune system plays a key role in preventing C. albicans infections, with both innate and adaptive immunity acting to restrict fungal colonization and growth. Commercially available products, such as antifungal creams, vaginal probiotics, and hygiene solutions, are practical options but often lack long-term efficacy. Persistent challenges, including resistance, patient noncompliance, and restricted access to emerging therapies, hinder comprehensive prevention and treatment efforts. Thus, future research should focus on promoting interdisciplinary approaches, integrating personalized medicine, and enhancing healthcare accessibility. This review intends to present the current state of the art within the abovementioned issues and to enhance the understanding of the multifactorial nature of C. albicans infections and advanced prevention strategies, which are essential to reduce the burden of vaginal candidiasis worldwide and improve patient quality of life outcomes. KEY POINTS: • Candida albicans pathogenesis involves biofilms, adherence, and phenotypic switching. • Vaccines, nanotechnology, and new drugs offer improved prevention and treatment. • Addressing antifungal resistance and patient compliance is key for prevention success.
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Affiliation(s)
- Margarida Faustino
- Biorbis Unipessoal Lda, Rua Diogo Botelho 1327, 4169 - 005, Porto, Portugal.
- Universidade Católica Portuguesa, CBQF-Centro de Biotecnologia e Química Fina-Laboratório Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169 - 005, Porto, Portugal.
| | - Carlos M H Ferreira
- Biorbis Unipessoal Lda, Rua Diogo Botelho 1327, 4169 - 005, Porto, Portugal
- Universidade Católica Portuguesa, CBQF-Centro de Biotecnologia e Química Fina-Laboratório Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169 - 005, Porto, Portugal
| | - Ana Margarida Pereira
- CBMA (Center of Molecular and Enviromental Biology), Department of Biology, Universidade do Minho, Campus Gualtar, 4710 - 057, Braga, Portugal
- IB-S (Institute of Science and Innovation for Bio-Sustainability), Campus de Gualtar, Universidade do Minho, 4710 - 057, Braga, Portugal
| | - Ana P Carvalho
- Biorbis Unipessoal Lda, Rua Diogo Botelho 1327, 4169 - 005, Porto, Portugal
- Universidade Católica Portuguesa, CBQF-Centro de Biotecnologia e Química Fina-Laboratório Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169 - 005, Porto, Portugal
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19
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Kaur E, Acharya V. Computational prediction of Homo sapiens-Candida albicans protein-protein interactions reveal key virulence factors using dual RNA-Seq data analysis. Arch Microbiol 2025; 207:115. [PMID: 40188396 DOI: 10.1007/s00203-025-04312-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2025] [Revised: 03/05/2025] [Accepted: 03/18/2025] [Indexed: 04/08/2025]
Abstract
A prevalent pathobiont, Candida albicans, accounts for approximately 70% of fungal infections worldwide owing to its virulence traits that culminate in devastating fatalities within healthcare facilities. Protein-protein interactions (PPIs) between Homo sapiens and C. albicans play a pivotal role in infection and disease progression. Additionally, scarcity of information on H. sapiens-C. albicans protein-protein interactions makes it difficult to understand the molecular mechanisms underlying infection and host immune responses. Investigating these PPIs can provide crucial insights into host-pathogen relationships and facilitate the development of novel therapeutic interventions. To address this challenge, we utilized computational techniques based on homology and domain to project 56,515 human-fungal pathogen protein-protein interactions (HF-PPIs) involving 6830 human and 486 C. albicans proteins. We have identified 16 key virulence factors of C. albicans, including SOD1, ERG10, GFA1, and VPS4, as potential therapeutic targets. As evidenced by dual RNA-Seq data acquired at various stages of infection such as 15, 30, 60, 120, and 240 min, these fungal genes interact with down-regulated human immunomodulatory genes specifically, ADRM1, DAXX, RYBP, SGTA, and SRGN. In addition to their intrinsically disordered regions, these human genes are particularly susceptible to fungal manipulation. Through the identification of experimentally validated virulence factors and their interaction partners, this investigation constructs HF-PPI between H. sapiens and C. albicans. Our knowledge of human-fungal pathogen protein-protein interactions will be improved by integrating computational and experimental data in order to facilitate the development of efficient fungal infection prevention and treatment protocols.
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Affiliation(s)
- Ekjot Kaur
- Artificial Intelligence for Computational Biology (AICoB) Laboratory, Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT), Palampur, Himachal Pradesh, 176061, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India
| | - Vishal Acharya
- Artificial Intelligence for Computational Biology (AICoB) Laboratory, Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT), Palampur, Himachal Pradesh, 176061, India.
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
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20
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Gomez-Artiguez L, de la Cámara-Fuentes S, Sun Z, Hernáez ML, Borrajo A, Pitarch A, Molero G, Monteoliva L, Moritz RL, Deutsch EW, Gil C. Candida albicans: A Comprehensive View of the Proteome. J Proteome Res 2025; 24:1636-1648. [PMID: 40084908 DOI: 10.1021/acs.jproteome.4c01020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2025]
Abstract
We describe a new release of the Candida albicans PeptideAtlas proteomics spectral resource (build 2024-03), providing a sequence coverage of 79.5% at the canonical protein level, matched mass spectrometry spectra, and experimental evidence identifying 3382 and 536 phosphorylated serine and threonine sites with false localization rates of 1% and 5.3%, respectively. We provide a tutorial on how to use the PeptideAtlas and associated tools to access this information. The C. albicans PeptideAtlas summary web page provides "Build overview", "PTM coverage", "Experiment contribution", and "Data set contribution" information. The protein and peptide information can also be accessed via the Candida Genome Database via hyperlinks on each protein page. This allows users to peruse identified peptides, protein coverage, post-translational modifications (PTMs), and experiments that identify each protein. Given the value of understanding the PTM landscape in the sequence of each protein, a more detailed explanation of how to interpret and analyze PTM results is provided in the PeptideAtlas of this important pathogen. Candida albicans PeptideAtlas web page: https://db.systemsbiology.net/sbeams/cgi/PeptideAtlas/buildDetails?atlas_build_id=578.
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Affiliation(s)
- Leticia Gomez-Artiguez
- Microbiology and Parasitology Department, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
| | | | - Zhi Sun
- Institute for Systems Biology, 401 Terry Ave North, Seattle, Washington 98109, United States
| | - María Luisa Hernáez
- Proteomics Unit, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
| | - Ana Borrajo
- Microbiology and Parasitology Department, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
| | - Aída Pitarch
- Microbiology and Parasitology Department, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
| | - Gloria Molero
- Microbiology and Parasitology Department, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
| | - Lucía Monteoliva
- Microbiology and Parasitology Department, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
| | - Robert L Moritz
- Institute for Systems Biology, 401 Terry Ave North, Seattle, Washington 98109, United States
| | - Eric W Deutsch
- Institute for Systems Biology, 401 Terry Ave North, Seattle, Washington 98109, United States
| | - Concha Gil
- Microbiology and Parasitology Department, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
- Proteomics Unit, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
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21
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Abreu-Pereira CA, Gorayb-Pereira AL, Jordão CC, Paro CB, Barbugli PA, Pavarina AC. Zerumbone enhances the photodynamic effect against biofilms of fluconazole-resistant Candida albicans clinical isolates. J Dent 2025; 155:105631. [PMID: 39956310 DOI: 10.1016/j.jdent.2025.105631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 02/12/2025] [Accepted: 02/14/2025] [Indexed: 02/18/2025] Open
Abstract
The aim was the evaluation of Zerumbone (ZER) associated with Photodithazine® (PDZ) mediated antimicrobial photodynamic therapy (aPDT) on fluconazole-resistant (CaR) and -susceptible (CaS) Candida albicans biofilms, and well as two fluconazole-resistant clinical isolates (R70 and R14). Biofilms (48 h) were treated with ZER (256 µg/mL) for 20 min, followed by the absence or presence of the photosensitizer (PDZ; 200 mg/L) and Light Emitting Diode (LED; 600 nm; 50 Jcm2), either alone or in combination, resulting in 8 treatment groups (Control; ZER; aPDT; PDZ; LED; ZER+aPDT; ZER+PDZ; ZER+LED; n = 12). The treatments were evaluated by colony-forming unit (CFU), total and insoluble biomass, extracellular matrix components (ECM) quantification [extracellular DNA (eDNA), proteins, alkali (ASP) and water-soluble polysaccharides (WSP)], and Confocal Laser Scanning Microscopy (CLSM). Data were subjected to three-way ANOVA with Bonferroni post-test (α 5 %). The combination of ZER and aPDT promoted a greater reduction of biofilms' components for all the strains evaluated (CaS, CaR, R14, R70). On average, ZER+aPDT group showed a 2.01 log10 (30 %) reduction in CFU counts, total biomass (30 %), insoluble biomass (33 %), and total protein (15 %). Additionally, there was a reduction in ECM components of the biofilms, such as insoluble proteins (24 %), WSP (68 %), ASP (26 %) and eDNA (60 %) compared to the control group. Images obtained through CLSM showed that the association of ZER+aPDT resulted in a higher content of dead cells. Treatment with ZER+aPDT enhanced the efficacy of photodynamic treatment on fluconazole-resistant C. albicans (including clinical isolates), representing an encouraging antifungal approach.
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Affiliation(s)
- César Augusto Abreu-Pereira
- Laboratory of Applied Microbiology, Department of Dental Materials and Prosthodontics, São Paulo State University (UNESP), School of Dentistry, Araraquara, São Paulo, Brazil
| | - Ana Luiza Gorayb-Pereira
- Laboratory of Applied Microbiology, Department of Dental Materials and Prosthodontics, São Paulo State University (UNESP), School of Dentistry, Araraquara, São Paulo, Brazil
| | - Cláudia Carolina Jordão
- Laboratory of Applied Microbiology, Department of Dental Materials and Prosthodontics, São Paulo State University (UNESP), School of Dentistry, Araraquara, São Paulo, Brazil
| | - Clara Brait Paro
- Laboratory of Applied Microbiology, Department of Dental Materials and Prosthodontics, São Paulo State University (UNESP), School of Dentistry, Araraquara, São Paulo, Brazil
| | - Paula Aboud Barbugli
- Laboratory of Applied Microbiology, Department of Dental Materials and Prosthodontics, São Paulo State University (UNESP), School of Dentistry, Araraquara, São Paulo, Brazil
| | - Ana Claudia Pavarina
- Laboratory of Applied Microbiology, Department of Dental Materials and Prosthodontics, São Paulo State University (UNESP), School of Dentistry, Araraquara, São Paulo, Brazil.
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22
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Bindu B, Manikandan A, Jeevitha S, Kunju JJ, Vijayalakshmi S. Imidazolidine-Based Aspartate Inhibitors for Candida Infections. Drug Dev Res 2025; 86:e70074. [PMID: 40159997 DOI: 10.1002/ddr.70074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2024] [Revised: 02/28/2025] [Accepted: 03/06/2025] [Indexed: 04/02/2025]
Abstract
The fungal infection gradually poses a life threat to mankind, candidiasis caused by Candida sp. is one among them. We describe the aspartate protease inhibition potentials of 12 sulfonyl-containing imidazolidines (5a-l) anti-candidal agents. Candida Albicans secretes aspartic proteases (Saps), one of its most important virulent agents. These hydrolytic enzymes are critical for both fungal physiological processes and host-fungus interactions. Compounds 5a-l were examined for their fungal aspartate protease inhibition apart from their anti-candida activity. These findings were equipped and validated in silico using molecular docking and in vitro enzyme inhibition assays. The study found that imidazolidine derivatives inhibited aspartic protease and exhibited anti-candida action. Conclusively, imidazolidines 5g, 5h, and 5j were perceived as the most potent anti-candida compounds and are presently being evaluated for their preclinical studies.
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Affiliation(s)
- B Bindu
- Department of Chemistry, Government Arts College, Coimbatore, India
| | - A Manikandan
- Center for Global Health Research, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha Medical College and Hospital, Chennai, India
| | - S Jeevitha
- Center for Global Health Research, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha Medical College and Hospital, Chennai, India
| | - Joe Jacob Kunju
- Center for Global Health Research, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha Medical College and Hospital, Chennai, India
| | - S Vijayalakshmi
- Department of Chemistry, Government Arts College, Coimbatore, India
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23
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Krishnan D, Aruna Senthil Kumar S, Jothipandiyan S, Yamuna Devi V, Suresh D, Nithyanand P. Exploring quinazoline-derived copper(I) complex coated intravaginal ring against vulvovaginal candidiasis causing Candida species. BIOFOULING 2025; 41:378-393. [PMID: 40265509 DOI: 10.1080/08927014.2025.2489479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 03/26/2025] [Accepted: 03/29/2025] [Indexed: 04/24/2025]
Abstract
Vulvovaginal candidiasis (VVC) is especially prevalent among intrauterine device (IUD) and intravaginal ring (IVR) users. Candida albicans is the leading causative agent of VVC followed by Candida glabrata. Ascribed to the increased drug resistance by Candida spp. to the currently available drugs, this study has focused on the novel quinazoline-derived copper(I) complexes as anti-candida agents. As a novel approach, a vaginal ring was coated with the best quinazoline-derived copper(I) complex, and biofilm disruption ability was evaluated. The coated vaginal ring eradicated 70% of preformed biofilms and also inhibited the hyphal transition of Candida albicans in a simulated vaginal fluid (SVF). The overall study validates the anti-biofilm and anti-virulent properties of the metal complex-coated vaginal ring using various microscopic studies.
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Affiliation(s)
- Dhesiga Krishnan
- Biofilm Biology Laboratory, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, India
| | - Sudaarsan Aruna Senthil Kumar
- Biofilm Biology Laboratory, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, India
| | - Sowndarya Jothipandiyan
- Biofilm Biology Laboratory, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, India
| | - Venkatesan Yamuna Devi
- Organometallics and Catalysis Laboratory, Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, India
| | - Devarajan Suresh
- Organometallics and Catalysis Laboratory, Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, India
| | - Paramasivam Nithyanand
- Biofilm Biology Laboratory, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, India
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24
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Sreepian PM, Popruk S, Rattanasinganchan P, Sreepian A. Comprehensive investigation of Litsea cubeba antibacterial and antifungal activities across solid, liquid, and vapor phases against key human pathogens. NARRA J 2025; 5:e1685. [PMID: 40352192 PMCID: PMC12059852 DOI: 10.52225/narra.v5i1.1685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Accepted: 02/22/2025] [Indexed: 05/14/2025]
Abstract
The escalating global incidence of antimicrobial resistance poses a significant public health challenge. In response, exploring alternative antimicrobial agents, particularly derived from plants, becomes crucial to alleviate the selective pressure exerted by conventional antibiotics. The aim of this study was to characterize the composition of essential oil extracted from Litsea cubeba fruits and to evaluate its antimicrobial potential, along with its major compound, across solid, liquid, and vapor phases. The antimicrobial activity was assessed against a diverse range of human pathogenic Gram-positive bacteria (n = 8), Gram-negative bacteria (n = 34), filamentous fungi (n = 2), and yeast (n = 1). Disk diffusion, broth macrodilution, and vapor-phase diffusion methods were employed. This study found that all phases of L. cubeba essential oil and purified limonene exhibited broad-spectrum bactericidal and fungicidal activities (solid-phase: inhibition zone diameter (IZD) 19 mm vs 14 mm; liquid-phase: minimum inhibitory concentration (MIC) 2.0 mg/mL vs 4.0 mg/mL; vapor-phase: IZD 90 mm vs 45 mm), with superior efficacy against filamentous fungi and yeast compared to bacteria (solid-phase: IZD 90 mm vs 17.5 mm; liquid-phase: MIC 2.0 mg/mL vs 0.06 mg/mL; vapor-phase: IZD 90 mm vs 12.5 mm; all p-values<0.05). Among bacteria, solid-phase L. cubeba essential oil demonstrated increased activity against Staphylococcus saprophyticus and Acinetobacter Iwoffii whereas liquid-phase L. cubeba essential oil had optimal activity against Streptococcus agalactiae and Elizabethkingia meningoceptica. Notably, Trichophyton rubrum, Nannizzia gypsea, and Candida albicans displayed high susceptibility to all phases of L. cubeba essential oil. These findings highlight the potential activity of L. cubeba essential oil, across its various phases, as a promising alternative antimicrobial agent against medically significant pathogens, providing essential baseline information for further exploration and development of L. cubeba essential oil in the pursuit of combating antimicrobial resistance.
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Affiliation(s)
| | - Supaluk Popruk
- Department of Protozoology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | | | - Apichai Sreepian
- Faculty of Medical Technology, Rangsit University, Pathum Thani, Thailand
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25
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Pruitt HM, Zhu JC, Riley SP, Shi M. The Hidden Fortress: A Comprehensive Review of Fungal Biofilms with Emphasis on Cryptococcus neoformans. J Fungi (Basel) 2025; 11:236. [PMID: 40137272 PMCID: PMC11943451 DOI: 10.3390/jof11030236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Revised: 03/14/2025] [Accepted: 03/17/2025] [Indexed: 03/27/2025] Open
Abstract
Biofilms are structurally organized communities of microorganisms that adhere to a variety of surfaces. These communities produce protective matrices consisting of polymeric polysaccharides, proteins, nucleic acids, and/or lipids that promote shared resistance to various environmental threats, including chemical, antibiotic, and immune insults. While algal and bacterial biofilms are more apparent in the scientific zeitgeist, many fungal pathogens also form biofilms. These surprisingly common biofilms are morphologically distinct from the multicellular molds and mushrooms normally associated with fungi and are instead an assemblage of single-celled organisms. As a collection of yeast and filamentous cells cloaked in an extracellular matrix, fungal biofilms are an extreme threat to public health, especially in conjunction with surgical implants. The encapsulated yeast, Cryptococcus neoformans, is an opportunistic pathogen that causes both pulmonary and disseminated infections, particularly in immunocompromised individuals. However, there is an emerging trend of cryptococcosis among otherwise healthy individuals. C. neoformans forms biofilms in diverse environments, including within human hosts. Notably, biofilm association correlates with increased expression of multiple virulence factors and increased resistance to both host defenses and antifungal treatments. Thus, it is crucial to develop novel strategies to combat fungal biofilms. In this review, we discuss the development and treatment of fungal biofilms, with a particular focus on C. neoformans.
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Affiliation(s)
| | | | - Sean P. Riley
- Department of Veterinary Medicine, Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA; (H.M.P.); (J.C.Z.)
| | - Meiqing Shi
- Department of Veterinary Medicine, Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA; (H.M.P.); (J.C.Z.)
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26
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Eskezia A, Teklemichael AM, Alemayehu T. The prevalence and risk factors of vaginal Candida species and group B Streptococcus colonization in pregnant women attending antenatal care at Hawassa university comprehensive specialized hospital in Hawassa City, Southern Ethiopia. BMC Pregnancy Childbirth 2025; 25:299. [PMID: 40098138 PMCID: PMC11912609 DOI: 10.1186/s12884-025-07402-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Accepted: 03/03/2025] [Indexed: 03/19/2025] Open
Abstract
BACKGROUND The global prevalence of vaginal candidiasis and group B streptococcus (GBS) colonization among pregnant women is significant and these pathogens are associated with adverse maternal and neonatal outcomes, including preterm birth, stillbirth, and neonatal infections. OBJECTIVE This study aimed to determine the magnitude and risk factors for vaginal Candida and GBS in pregnant women who were attending antenatal care at Hawassa University Compressive Specialized Hospital from July October 2021. METHOD A Hospital-based, cross-sectional study was conducted using microscopy, culture, germ tube, and biochemical tests on vaginal swab samples from 110 volunteer pregnant women. A structured questionnaire was used to collect data on perceived risk factors. Data was analyzed using SPSS version 22, and an odds ratio at a 95% confidence interval with p < 0.05 was used to interpret the risk factors. RESULTS Candida species was identified in 33 (30%) pregnant women, whereas, GBS colonization was not detected in any of them. Of the vaginal Candida species, 17 (51.52%) were Candida albicans and 16 (48.48%) were non-albicans Candida. Symptomatic vaginal candidiasis was diagnosed in only four women. The most important predictors of vaginal Candida colonization were parity of two and underwear replacement once a day. CONCLUSION Based on these findings, screening for vaginal candidiasis and prophylactic treatment should be considered for young, multiparous, pregnant women in their third trimester, if supported clinically.
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Affiliation(s)
- Atenaf Eskezia
- Philipos Education and Training Center, Hawassa City, Ethiopia
| | | | - Tsegaye Alemayehu
- School of Medical Laboratory Sciences, Hawassa University, P.O.Box 5, Hawassa City, Ethiopia
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27
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Guerra RNM, Oliveira AS, Farias JR, Franco DCG, Santos PG, Barbosa NT, Muniz SB, Abreu AG, Nascimento FRF. Anacardiaceae Family: Effect of Isolated Compounds and Other Identified Phytochemicals Against Clinically Relevant Candida Species-A Short Review. Antibiotics (Basel) 2025; 14:308. [PMID: 40149118 PMCID: PMC11939211 DOI: 10.3390/antibiotics14030308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2025] [Revised: 03/09/2025] [Accepted: 03/14/2025] [Indexed: 03/29/2025] Open
Abstract
Background: The increased rates of common fungal diseases are a constant challenge. Therefore, the search for plant-based compounds with antifungal activity, particularly ones against Candida species, is always relevant in the medical context. However, most of the studies have focused on screening the antifungal activity of extracts rather than isolated compounds. Based on this, we aimed to analyze and organize a comprehensive overview of the antifungal and other biological activities of isolated compounds found in Anacardiaceae family vegetal species, covering mechanisms of action and potential therapeutic applications. Results: The extracts, essential oils, and compounds are frequently assayed for anti-Candida activity using the in vitro minimum inhibitory concentration (MIC), minimum fungicide concentration (MFC), and halo inhibition assays. Candida albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei, and C. guilliermondii were the most tested fungus species. Essential oils were the most used form (37% of the studies). The isolated compounds included shikimic acid, 2-hydroxy-1,8-cineole β-D-glucopyranoside, myricitrin, cardanol, estragole, trans-anethole, β-caryophyllene, myrcene, catechin-3-O-rhamnoside, β-sitosterol-3-O-glucoside, 24Z-isomasticadienolic acid, oleanolic acid, pistagremic acid, apigenin, sakuranetin, oleanolic aldehyde, and integriside. Conclusions: Our data indicate that the compounds isolated from Anacardiaceae species show promise for developing new therapeutic antifungal drugs, mainly if we consider their other biological activities, including anti-inflammatory, antioxidant, and apoptotic effects. In this context, they may be candidates for future treatments of fungal infections, especially in combination with conventional antifungals or when used in nanostructured formulations, which may result in a new avenue of using plant extracts and isolated compounds.
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Affiliation(s)
- Rosane Nassar Meireles Guerra
- Laboratorio de Imunofisiologia, Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal do Maranhão, Campus Bacanga, Av. dos Portugueses, 1966, São Luís 65080-805, Brazil
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28
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Ugochukwu ICI, Mendoza-Roldan JA, Miglianti M, Palazzo N, Odigie AE, Otranto D, Cafarchia C. Virulence profile of pathogenic yeasts from snakes: Alternative ways for antifungal strategies. PLoS One 2025; 20:e0318703. [PMID: 40072936 PMCID: PMC11902152 DOI: 10.1371/journal.pone.0318703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Accepted: 01/20/2025] [Indexed: 03/14/2025] Open
Abstract
Reptiles may act as reservoirs or spreaders of potential pathogenic microorganisms including Candida yeasts. While the epidemiology of yeast species has been thoroughly studied, the virulence profile of isolated species is not well investigated. Therefore, this study aimed to assess the haemolytic, phospholipase, lipase activities and biofilm formation of yeasts isolated from the cloacal swabs of venomous snakes from Marrakech, Morocco (Group I, n = 40) and from non-venomous snakes from Cocullo, Italy (Group II, n = 32). All the isolated yeasts from Group 1 showed low production of lipase (Lz ≥ 0.90) and haemolysin (Hz ≥ 0.90), and only 35% of them were low phospholipase (Pz) producers (Pz > 0.90). In contrast, all the yeasts from Group 2 produced enzymes and more than 62% produced high amounts of enzymes (Pz ≤ 0.64; Lz ≤ 0.69; Hz ≤ 0.69). Data show that yeasts from snakes were able to produce virulence factors, which vary according to the yeast species and the hosts or their origin, thus suggesting the potential role of snakes in harboring and spreading pathogenic yeasts in the environment. Since the virulence profile was lower in venomous snakes than that in non-venomous ones, we discussed that it may be affected by the venom composition. This will pave the way for fungal infection control, alternative to antifungal drugs in order to overcome resistance phenomena.
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Affiliation(s)
- Iniobong Chukwuebuka I. Ugochukwu
- Department of Veterinary Medicine, University of Bari Aldo Moro, Valenzano, Bari, Italy
- Department of Veterinary Pathology, University of Nigeria, Nsukka, Nsukka, Nigeria
| | | | - Mara Miglianti
- Department of Veterinary Medicine, University of Bari Aldo Moro, Valenzano, Bari, Italy
| | - Natalizia Palazzo
- Department of Veterinary Medicine, University of Bari Aldo Moro, Valenzano, Bari, Italy
| | | | - Domenico Otranto
- Department of Veterinary Medicine, University of Bari Aldo Moro, Valenzano, Bari, Italy
- Department of Veterinary Clinical Sciences, City University of Hong Kong, Hong Kong, SAR China
| | - Claudia Cafarchia
- Department of Veterinary Medicine, University of Bari Aldo Moro, Valenzano, Bari, Italy
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29
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Ma Y, Zhou Y, Jia T, Zhuang Z, Xue P, Yang L. Deciphering the role of mitochondria in human fungal drug resistance. Mycology 2025:1-14. [DOI: 10.1080/21501203.2025.2473507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Accepted: 02/24/2025] [Indexed: 05/04/2025] Open
Affiliation(s)
| | | | | | | | | | - Liang Yang
- Southern University of Science and Technology
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30
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Mahboub HH, Rahman ANA, Elazab ST, Abdelwarith AA, Younis EM, Shaalan M, Aziz EK, Sobh MS, Yousefi M, Ismail SH, Davies SJ, Gaballa MMS. Nano-chitosan hydrogel alleviates Candida albicans-induced health alterations in Nile tilapia (Oreochromis niloticus): antioxidant response, neuro-behaviors, hepato-renal functions, and histopathological investigation. BMC Vet Res 2025; 21:159. [PMID: 40057767 PMCID: PMC11889809 DOI: 10.1186/s12917-025-04568-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 02/05/2025] [Indexed: 05/13/2025] Open
Abstract
BACKGROUND Candida albicans infection induces economic losses in aquaculture practices. Currently, the success of the nanotechnology field has gained more consideration in the aquaculture sector as it bestows favorable impacts in remedies in comparison to traditional practices. OBJECTIVE The present study was conducted to assess the role of nano chitosan gel (NCG) exposure via water in managing the deteriorating impacts triggered by C. albicans in Nile tilapia, Oreochromis niloticus. Hepato-renal function, behavioral and stress response, neurological function, hepatic antioxidant/oxidant status, and histopathological architectures were investigated. METHODS A total of 160 fish (average weight: 50.00 ± 6.30 g) were randomly assigned to four groups, each with four replicates: control, NCG, C. albicans, and NCG + C. albicans. The NCG was applied as bath treatment at a concentration of 75 µg/L for ten days. RESULTS The outcomes demonstrated that the C. albicans challenged fish exhibited obvious behavioral alterations including loss of equilibrium, surfacing, abnormal swimming and movement, and aggression. Infection with C. albicans caused an elevation in hepato-renal biomarkers (alanine and aspartate aminotransferases, alkaline phosphatase, urea, and creatinine), stress-related indices (glucose, cortisol, nor-epinephrine, and 8-hydroxy-2-deoxyguanosine), and lipid peroxides (malondialdehyde). Moreover, it caused a noticeable decline in the hepatic antioxidant indices (total antioxidant capacity and reduced glutathione content) and acetylcholinesterase activity. The hepatic, renal, and brain architectures were severely damaged by the C. albicans challenge, exhibiting significant fatty changes, necrosis, vacuolation, and congestion. Remarkably, the aqueous application of NCG in the C. albicans-challenged fish ameliorated all the aforementioned biomarkers and facilitated the regeneration of histopathological changes. CONCLUSION Overall, the application of NCG in the aquatic environment is an effective tool for managing C. albicans infection in Nile tilapia. Moreover, it can be utilized in combating stress conditions in the aquaculture sector.
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Affiliation(s)
- Heba H Mahboub
- Department of Aquatic Animal Medicine, Faculty of Veterinary Medicine, Zagazig University, PO Box 44511, Zagazig, Sharkia, Egypt.
| | - Afaf N Abdel Rahman
- Department of Aquatic Animal Medicine, Faculty of Veterinary Medicine, Zagazig University, PO Box 44511, Zagazig, Sharkia, Egypt
| | - Sara T Elazab
- Department of Pharmacology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, Egypt
| | - Abdelwahab A Abdelwarith
- Department of Zoology, College of Science, King Saud University, PO Box 2455, Riyadh, 11451, Saudi Arabia
| | - Elsayed M Younis
- Department of Zoology, College of Science, King Saud University, PO Box 2455, Riyadh, 11451, Saudi Arabia
| | - Mohamed Shaalan
- Department of Pathology, Faculty of Veterinary Medicine, Cairo University, PO Box 12211, Giza, Egypt.
- Polymer Institute, Slovak Academy of Sciences, Dúbravská cesta 9, Bratislava, 84541, Slovakia.
| | - Enas K Aziz
- Department of Husbandry and Animal Wealth Development, Faculty of Veterinary Medicine, University of Sadat City, PO Box 32958, Sadat City, Egypt
| | - Mohammed S Sobh
- Pathology Department, Faculty of Veterinary Medicine, Zagazig University, PO Box 44511, Zagazig, Sharkia, Egypt
| | - Morteza Yousefi
- Department of Veterinary Medicine, RUDN University, Miklukho-Maklaya St, Moscow, 117198, Russia
| | - Sameh H Ismail
- Faculty of Nanotechnology for Postgraduate Studies, Cairo University, Sheikh Zayed Branch Campus, PO Box 12588, Sheikh Zayed City, Giza, Egypt
| | - Simon J Davies
- Aquaculture Nutrition Research Unit ANRU, Carna Research Station, Ryan Institute, College of Science and Engineering, University of Galway, Galway, H91V8Y1, Ireland
| | - Mohamed M S Gaballa
- Department of Pathology, Faculty of Veterinary Medicine, Benha University, PO Box 13736, Benha, Toukh, Egypt
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31
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Srikanth Y, Reddy DH, Anusha VL, Dumala N, Viswanadh MK, Chakravarthi G, Nalluri BN, Yadagiri G, Ramakrishna K. Unveiling the Multifaceted Pharmacological Actions of Indole-3-Carbinol and Diindolylmethane: A Comprehensive Review. PLANTS (BASEL, SWITZERLAND) 2025; 14:827. [PMID: 40094833 PMCID: PMC11902694 DOI: 10.3390/plants14050827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Revised: 02/28/2025] [Accepted: 03/04/2025] [Indexed: 03/19/2025]
Abstract
Cruciferae family vegetables are remarkably high in phytochemicals such as Indole-3-carbinol (I3C) and Diindolylmethane (DIM), which are widely known as nutritional supplements. I3C and DIM have been studied extensively in different types of cancers like breast, prostate, endometrial, colorectal, gallbladder, hepatic, and cervical, as well as cancers in other tissues. In this review, we summarized the protective effects of I3C and DIM against cardiovascular, neurological, reproductive, metabolic, bone, respiratory, liver, and immune diseases, infections, and drug- and radiation-induced toxicities. Experimental evidence suggests that I3C and DIM offer protection due to their antioxidant, anti-inflammatory, antiapoptotic, immunomodulatory, and xenobiotic properties. Apart from the beneficial effects, the present review also discusses the possible toxicities of I3C and DIM that are reported in various preclinical investigations. So far, most of the reports about I3C and DIM protective effects against various diseases are only from preclinical studies; this emphasizes the dire need for large-scale clinical trials on these phytochemicals against human diseases. Further, in-depth research is required to improve the bioavailability of these two phytochemicals to achieve the desirable protective effects. Overall, our review emphasizes that I3C and DIM may become potential drug candidates for combating dreadful human diseases.
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Affiliation(s)
- Yadava Srikanth
- KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram 522302, India; (Y.S.); (D.H.R.); (V.L.A.); (N.D.); (M.K.V.); (G.C.); (B.N.N.)
| | - Dontiboina Harikrishna Reddy
- KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram 522302, India; (Y.S.); (D.H.R.); (V.L.A.); (N.D.); (M.K.V.); (G.C.); (B.N.N.)
| | - Vinjavarapu Lakshmi Anusha
- KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram 522302, India; (Y.S.); (D.H.R.); (V.L.A.); (N.D.); (M.K.V.); (G.C.); (B.N.N.)
| | - Naresh Dumala
- KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram 522302, India; (Y.S.); (D.H.R.); (V.L.A.); (N.D.); (M.K.V.); (G.C.); (B.N.N.)
| | - Matte Kasi Viswanadh
- KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram 522302, India; (Y.S.); (D.H.R.); (V.L.A.); (N.D.); (M.K.V.); (G.C.); (B.N.N.)
| | - Guntupalli Chakravarthi
- KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram 522302, India; (Y.S.); (D.H.R.); (V.L.A.); (N.D.); (M.K.V.); (G.C.); (B.N.N.)
| | - Buchi N. Nalluri
- KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram 522302, India; (Y.S.); (D.H.R.); (V.L.A.); (N.D.); (M.K.V.); (G.C.); (B.N.N.)
| | - Ganesh Yadagiri
- Obstetrics and Gynecology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Kakarla Ramakrishna
- KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram 522302, India; (Y.S.); (D.H.R.); (V.L.A.); (N.D.); (M.K.V.); (G.C.); (B.N.N.)
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Nath AG, Vaiphei KK, Kumar A, Basrani S, Jadhav A, Chakravarti R, Ghosh D, Bansal KK, Gulbake A. Dual Drug Loaded Topical Cubosomal Gel Against Candida Albicans: An In Vitro and In Vivo Proof of Concept. AAPS PharmSciTech 2025; 26:77. [PMID: 40045107 DOI: 10.1208/s12249-025-03070-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Accepted: 02/13/2025] [Indexed: 05/13/2025] Open
Abstract
Dual drug approaches are gaining research interest owing to the reduction of drug resistance and additive or synergistic effects in treating fungal infections caused by Candida albicans. The present study includes the combination of ketoconazole (KTC) and eugenol (EGN) co-embedded cubosomes (KTC-EGN-CBs) for the effective treatment of candidiasis.The bio-membrane-typical framework of the cubic phase in CBs can help retain both drugs leading to enhancement of antifungal activity. KTC-EGN-CBs were developed by high-speed homogenization, followed by the probe sonication. The optimized KTC-EGN-CBs depicted lower particle size (138.8 ± 1.03 nm) and PdI (0.260 ± 0.006) with a high entrapment efficiency of KTC (79.73 ± 1.21%) and EGN (90.92 ± 2.53%). Further, KTC-EGN-CBs were loaded into the hydrogel system for ease of topical application. The ex vivo diffusion study depicted the CBs helping the KTC and EGN to exhibit significantly higher permeation and retention owing to the resemblance in cubic structure with the skin. Additionally, the in vitro antifungal study of KTC-EGN-CBs resulted in a higher zone of inhibition when compared to the plain drugs against Candida albicans. Furthermore, the effectiveness of cubosomal formulation was observed in the inhibition of planktonic growth, yeast to hyphal formation, biofilm formation, and ROS production. The antifungal activity of KTC-EGN-CBs was found to be more prominent in the infected silkworm model than the plain KTC-EGN. The cell cytotoxicity study on human keratinocyte cells and the irritation study on the hen's egg test-chorioallantoic membrane assay revealed the non-cytotoxic and non-irritant nature of the prepared cubosomes. In a nutshell, these findings demonstrated CBs as a promising carrier for KTC and EGN to effectively treat candidiasis.
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Affiliation(s)
- A Gowri Nath
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research Guwahati, Assam, 781101, India
| | - Klaudi K Vaiphei
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research Guwahati, Assam, 781101, India
| | - Ankaj Kumar
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research Guwahati, Assam, 781101, India
| | - Sargun Basrani
- Department of Medical Biotechnology, CIR, DY Patil Education Society, Institution Deemed to be University, Kolhapur, India
| | - Ashwini Jadhav
- Department of Medical Biotechnology, CIR, DY Patil Education Society, Institution Deemed to be University, Kolhapur, India
| | - Rudra Chakravarti
- Department of Natural Products, National Institute of Pharmaceutical Education and Research, Kolkata, West Bengal, 700054, India
| | - Dipanjan Ghosh
- Department of Natural Products, National Institute of Pharmaceutical Education and Research, Kolkata, West Bengal, 700054, India
| | - Kuldeep K Bansal
- Laboratory of Molecular Science and Engineering, Åbo Akademi University, Aurum, Henrikinkatu 2, Turku, 20500, Finland
- Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku, 20520, Finland
| | - Arvind Gulbake
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research Guwahati, Assam, 781101, India.
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Mousa HRF, Abiko Y, Washio J, Sato S, Takahashi N. Candida albicans and NCAC species: acidogenic and fluoride-resistant oral inhabitants. J Oral Microbiol 2025; 17:2473938. [PMID: 40052107 PMCID: PMC11884091 DOI: 10.1080/20002297.2025.2473938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 02/05/2025] [Accepted: 02/19/2025] [Indexed: 03/09/2025] Open
Abstract
Objective Although Candida species are thought to contribute to dental caries, their acid production under anaerobic conditions and susceptibility to fluoride have not been thoroughly studied. We therefore investigated the growth, acid production, and effect of fluoride on Candida species. Methods Aerobic growth, acid production from glucose and its end-products under aerobic and anaerobic conditions, and enolase activity were measured in C. albicans and non-Candida-albicans-Candida (NCAC) species (C. tropicalis, C. parapsilosis, C. maltosa, and C. glabrata), and the effect of fluoride on these abilities was evaluated. Results All Candida species produced acids under aerobic and anaerobic conditions, and acetate and TCA cycle metabolites were detected. However, these organic acids only accounted for 1.9-57.6% of the acids produced. Up to 80 mM fluoride hardly inhibited growth and did not inhibit acid production except for C. glabrata, despite the low 50% inhibitory fluoride concentration of 0.19-0.34 mM for enolase. Conclusion Candida species produced acids under aerobic and anaerobic conditions, indicating their significant cariogenicity. Their growth and acid production were highly fluoride-resistant, whereas their enolase was fluoride-sensitive, suggesting mechanisms for maintaining low intracellular fluoride. The mechanisms underlying the fluoride resistance remain underexplored. Approaches other than fluoride may be needed to control Candida-associated caries.
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Affiliation(s)
- Haneen Raafat Fathi Mousa
- Division of Oral Ecology and Biochemistry, Tohoku University Graduate School of Dentistry, Sendai, Japan
- Pediatric Dentistry and Dental Public Health Department, Faculty of Dentistry, Ain Shams University, Cairo, Egypt
| | - Yuki Abiko
- Division of Oral Ecology and Biochemistry, Tohoku University Graduate School of Dentistry, Sendai, Japan
| | - Jumpei Washio
- Division of Oral Ecology and Biochemistry, Tohoku University Graduate School of Dentistry, Sendai, Japan
| | - Satoko Sato
- Division of Oral Ecology and Biochemistry, Tohoku University Graduate School of Dentistry, Sendai, Japan
| | - Nobuhiro Takahashi
- Division of Oral Ecology and Biochemistry, Tohoku University Graduate School of Dentistry, Sendai, Japan
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Jabeen S, Khan MU, Ejaz H, Waqar S, Farhana A, Alruwaili M, Alruwaili Y, Abdalla AE, Mudassar S, Ali Q. Identifying novel inhibitors against drug-resistant mutant CYP-51 Candida albicans: A computational study to combat fungal infections. PLoS One 2025; 20:e0318539. [PMID: 40036223 PMCID: PMC11878927 DOI: 10.1371/journal.pone.0318539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Accepted: 01/19/2025] [Indexed: 03/06/2025] Open
Abstract
Candida albicans (C. albicans) is an opportunistic pathogen in immunocompromised individuals and a normal inhabitant of the oral cavity, throat, gastrointestinal tract, and genitourinary system among health populations. Our study focused on identifying new inhibitors capable of binding to the mutant cytochrome P450 family 51 (CYP-51) protein and intended to be effective against resistant C. albicans infections. The pharmacophore ligand-based model was used for the virtual screening of compound libraries. Molecular docking was performed on Maestro, Schrodinger. ADMET analysis was performed to check drug-likeness properties. Density function theory (DFT) calculations, molecular dynamic (MD) simulation, and free binding energy (MMPBSA) were also calculated. For docking, six compounds were selected from 11,022 hits from PubChem libraries, which showed the best interaction with mutant CYP-51 and were identified by pharmacophore mapping performed with the Pharma IT tool. Each of the six compounds was docked into the active site of the mutant CYP-51 protein. Overall, CP-3 exhibited significant binding affinity (-10.70 kcal/mol) as well as, showed good ADMET characteristics such as drug-likeness, absorption, distribution, metabolism, excretion, and toxicity. The lead compound, CP-3, was further used for MD simulation to observe the dynamic behavior of the complex in the active site of the mutant CYP-51 protein. Computational studies indicated that CP-3 could be a useful antagonist for the mutant protein, CYP-51. This study used computational approaches to identify potential inhibitors of C. albicans by targeting CYP-51 for antifungal drug development. Further invitro and in vivo studies are needed to evaluate its pharmacokinetic properties and efficacy as a novel antifungal drug.
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Affiliation(s)
- Saadia Jabeen
- Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan
| | - Muhammad Umer Khan
- Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan
| | - Hasan Ejaz
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia
| | - Shakeel Waqar
- Department of Pathology and Laboratory Medicine, Auckland City Hospital, Auckland, New Zealand
| | - Aisha Farhana
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia
| | - Muharib Alruwaili
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia
| | - Yasir Alruwaili
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia
- Sustainable Development Research and Innovation Center, Deanship of Graduate Studies and Scientific Research, Jouf University, Sakaka, Saudi Arabia
| | - Abualgasim Elgaili Abdalla
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia
| | - Sahar Mudassar
- Department of Pathology, Rashid Latif Medical College, Lahore, Pakistan
| | - Qurban Ali
- Department of Plant Breeding and Genetics, Faculty of Agricultural Sciences, University of the Punjab, Lahore, Pakistan
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Palacios YB, Simonetti SO, Chavez CH, Álvarez MG, Cordero PV, Cuello EA, González López EJ, Larghi EL, Agazzi ML, Durantini EN, Heredia DA. "Illuminated Glycoporphyrins": A photodynamic approach for Candida albicans inactivation. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY. B, BIOLOGY 2025; 264:113105. [PMID: 39922039 DOI: 10.1016/j.jphotobiol.2025.113105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 12/23/2024] [Accepted: 01/21/2025] [Indexed: 02/10/2025]
Abstract
The continuous increase in the incidence of invasive mycoses, particularly those caused by Candida albicans, is a relevant health issue worldwide due to the lack of effective antifungals and the constant emergence of resistant strains. One of the most promising therapies to treat infections caused by resistant microorganisms is photodynamic inactivation (PDI). The development of novel photosensitizers (PSs) with suitable properties is a key factor to consider when optimizing this therapy. In this work, we designed, synthesized, and characterized four glycoporphyrins functionalized with S-galactose (acetylated and deacetylated) and varying the number of tertiary amino groups as precursors of cationic centers, which can be activated by protonation at physiological pH. The amino and glycosyl groups were introduced to enhance interaction with the microbial cell wall, increase hydrophilicity, and evaluate their combined effect on PS efficiency in photoinactivation. All derivatives presented the characteristic absorption and emission properties of the porphyrin macrocycle. Moreover, the glycoporphyrins were capable of generating singlet oxygen and superoxide anion radical. The photophysical and photodynamic properties were not affected by the different substitution patterns on the porphyrin core. PDI treatments of C. albicans cultures, treated with 5 μM of the PS and irradiated for 30 min, produced cellular inactivation of ∼3.5 log for glycoporphyrins with cationic centers. Furthermore, PDI of C. albicans mediated by glycoporphyrins was potentiated by the addition of KI. Under these conditions, a significant enhancement in cellular death was observed, achieving complete eradication of the treated cell suspensions. Moreover, glycoporphyrins containing pH-activable groups, combined with KI, showed outstanding efficacy against C. albicans pseudohyphae. These in vitro findings underscore the significant impact of substitution patterns on antimicrobial action. To our knowledge, this study marks the first application of glycosylated porphyrin derivatives containing pH-activatable cationic groups in the photoinactivation of C. albicans, paving the way for the development of novel derivatives with potential applications as effective antifungal PSs.
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Affiliation(s)
- Yohana B Palacios
- IDAS-CONICET, Departamento de Química, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Agencia Postal Nro. 3, X5804BYA Río Cuarto, Córdoba, Argentina
| | - Sebastián O Simonetti
- IQUIR-CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK Rosario, Argentina
| | - Claudia Hernández Chavez
- IDAS-CONICET, Departamento de Química, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Agencia Postal Nro. 3, X5804BYA Río Cuarto, Córdoba, Argentina
| | - María G Álvarez
- IDAS-CONICET, Departamento de Química, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Agencia Postal Nro. 3, X5804BYA Río Cuarto, Córdoba, Argentina
| | - Paula V Cordero
- IDAS-CONICET, Departamento de Química, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Agencia Postal Nro. 3, X5804BYA Río Cuarto, Córdoba, Argentina
| | - Emma A Cuello
- IDAS-CONICET, Departamento de Química, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Agencia Postal Nro. 3, X5804BYA Río Cuarto, Córdoba, Argentina
| | - Edwin J González López
- IDAS-CONICET, Departamento de Química, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Agencia Postal Nro. 3, X5804BYA Río Cuarto, Córdoba, Argentina
| | - Enrique L Larghi
- IQUIR-CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK Rosario, Argentina
| | - Maximiliano L Agazzi
- IDAS-CONICET, Departamento de Química, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Agencia Postal Nro. 3, X5804BYA Río Cuarto, Córdoba, Argentina
| | - Edgardo N Durantini
- IDAS-CONICET, Departamento de Química, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Agencia Postal Nro. 3, X5804BYA Río Cuarto, Córdoba, Argentina.
| | - Daniel A Heredia
- IDAS-CONICET, Departamento de Química, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Agencia Postal Nro. 3, X5804BYA Río Cuarto, Córdoba, Argentina.
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Kumar P, Parveen, Khatoon S, Kumar M, Raj N, Harsha, Solanki R, Manzoor N, Kapur MK. In vitro antifungal activity analysis of Streptomyces sp. strain 196 against Candida albicans and Aspergillus flavus. Int Microbiol 2025; 28:553-562. [PMID: 39068607 DOI: 10.1007/s10123-024-00562-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 05/12/2024] [Accepted: 07/22/2024] [Indexed: 07/30/2024]
Abstract
Numerous bioactive compounds have been reported to be produced by the members of the genus Streptomyces. During our previous studies, Streptomyces sp. strain 196 was tested for its antimicrobial activity, and bioactive compounds produced by this strain were characterized LC-MS and 1H NMR. To examine the antifungal potential of strain 196 is the goal of the current investigation. Present investigation is focused on exploring antifungal activity of extract of strain 196 (196EA) on membrane disruption potential against two fungi Candida albicans ATCC 90028 and Aspergillus flavus ITCC 5599. Results revealed that the MIC value is higher for A. flavus than for C. albicans which is 450 µg/mL and 250 µg/mL, respectively. Disc diffusion and spot assay also correspond to the values of the MIC for their respective pathogen. In growth curve analysis, lag and log phase are significantly affected by the extract of strain 196. The effects of extract from strain 196 on plasma membrane disruption of Candida albicans and Aspergillus flavus were analyzed in terms of ergosterol quantification assay, cellular leakage, proton efflux measurement (PM-ATPase), plasma membrane integrity assay (PI), and DNA damage assay (DAPI). Results shown that the extract of strain 196 has the potential to inhibit the cell membrane of the both pathogenic fungi which was further confirmed with the help of scanning electron microscopic (SEM) studies.
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Affiliation(s)
- Prateek Kumar
- Department of Zoology, University of Allahabad, Uttar Pradesh, Prayagraj, 211 002, India
| | - Parveen
- Medical Mycology Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, 110025, India
| | - Shabana Khatoon
- Medical Mycology Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, 110025, India
| | - Munendra Kumar
- Department of Zoology, Rajiv Gandhi University, Doimukh, 791112, Arunachal Pradesh, India
| | - Nafis Raj
- Medical Mycology Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, 110025, India
| | - Harsha
- Microbial Technology Lab, Acharya Narendra Dev College, University of Delhi, New Delhi, 110 019, India
| | - Renu Solanki
- Deen Dayal Upadhyaya College, University of Delhi, New Delhi, 110 078, India
| | - Nikhat Manzoor
- Medical Mycology Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, 110025, India.
| | - Monisha Khanna Kapur
- Microbial Technology Lab, Acharya Narendra Dev College, University of Delhi, New Delhi, 110 019, India.
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Turkbey M, Karaguzel D, Uzunkaya AD, Aracagok YD, Karaaslan C. The immune response of upper and lower airway epithelial cells to Aspergillus fumigatus and Candida albicans-derived β-glucan in Th17 type cytokine environment. Arch Microbiol 2025; 207:70. [PMID: 39992431 DOI: 10.1007/s00203-025-04266-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 01/24/2025] [Accepted: 02/03/2025] [Indexed: 02/25/2025]
Abstract
The fungal cell wall component β-glucan activates inflammation via the Dectin-1 receptor and IL-17 coordinates the antifungal immunity. However, the molecular crosstalk between IL-17, Dectin-1, and β-glucan in epithelial cells and fungal immunity remains unclear. We investigated the impact of A.fumigatus-derived β-glucan (AFBG) and C.albicans-derived β-glucan (CABG) on Dectin-1 and cytokines in nasal epithelial cells (NECs) and bronchial epithelial cells (BECs) in the presence of IL-17. CABG reduced BEC viability more than AFBG despite similar Dectin-1 expression. IL-17 reduced β-glucan-dependent Dectin-1 expression in NECs but increased it in BECs after 12 h. AFBG synergized with IL-17, enhancing pro-inflammatory cytokines and chemokine expressions. IL-6 and IL-8 production increased in the presence of IL-17. Th17 cytokine influenced the Dectin-1 response to fungal β-glucan in NECs and BECs, impacting the initiation and nature of epithelial cell reactions to AFBG and CABG. Uncovering the molecular mechanisms of fungal β-glucans in the respiratory tract could lead to novel strategies for preventing fungal diseases.
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Affiliation(s)
- Murat Turkbey
- Department of Biology, Molecular Biology Section, Faculty of Science, Hacettepe University, 06800, Ankara, Türkiye
| | - Dilara Karaguzel
- Department of Biology, Molecular Biology Section, Faculty of Science, Hacettepe University, 06800, Ankara, Türkiye
| | - Ali Doruk Uzunkaya
- Department of Biology, Molecular Biology Section, Faculty of Science, Hacettepe University, 06800, Ankara, Türkiye
| | - Yusuf Doruk Aracagok
- Department of Biology, Biotechnology Section, Faculty of Science, Hacettepe University, 06800, Ankara, Türkiye
| | - Cagatay Karaaslan
- Department of Biology, Molecular Biology Section, Faculty of Science, Hacettepe University, 06800, Ankara, Türkiye.
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Harine A, Ranjani S, Hemalatha S. Antifungal efficacy of Citrusfusion mediated silver nanoparticles in Candida species. BMC Biotechnol 2025; 25:18. [PMID: 39979871 PMCID: PMC11841014 DOI: 10.1186/s12896-025-00952-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 02/10/2025] [Accepted: 02/13/2025] [Indexed: 02/22/2025] Open
Abstract
BACKGROUND Candida species are commensal fungi that can become opportunistic pathogens under specific host and environmental conditions. The emergence of multidrug-resistant Candida strains poses a significant challenge. Nanotechnology represents a cutting-edge field offering precise and targeted delivery systems for combating fungal infections, leveraging the unique properties of plant-derived bioactive compounds. This investigation employed a biogenic approach utilizing polyherbal leaf extracts from Citrus limon and Citrus medica, known for their abundant Citral content. RESULTS Citrus sp. extracts were used to synthesize Citrusfusion silver nanoparticles (CitAgNPs) through a green synthesis method. Characterization of CitAgNPs was carried out using advanced analytical methods ensuring the quality, uniformity, size, and charge. The synthesized CitAgNPs exhibited non toxic effect when tested on Vigna radiata and Danio rerio, highlighting their potential for sustainability and safe therapeutic use. Antifungal assays demonstrated the potent efficacy of CitAgNPs in various Candida strains, with low MIC and MFC. CitAgNPs exhibited remarkable biofilm inhibition capabilities and elucidated specific mechanisms of action in Candida species, surpassing the performance of fluconazole. CONCLUSION This study underscores the immense potential of nanotechnology-driven approaches harnessing Citrus leaf extract for synthesizing highly effective antifungal nanoparticles. The fusion of biogenic nanoparticles with Citrus bioactive compounds presents a sustainable strategy for addressing the escalating challenge of azole-resistant Candida infections. The research outcomes suggest that CitAgNPs have promising applications in inhibiting Candida biofilms, offering potential solutions for infections caused by diaper rashes and onychomycosis, providing safe and effective alternatives to antifungal therapies.
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Affiliation(s)
- A Harine
- School of Life Sciences, B. S. Abdur Rahman Crescent Institute of Science and Technology, Vandalur, Chennai, Tamil Nadu, 600048, India
| | - S Ranjani
- School of Life Sciences, B. S. Abdur Rahman Crescent Institute of Science and Technology, Vandalur, Chennai, Tamil Nadu, 600048, India
| | - S Hemalatha
- School of Life Sciences, B. S. Abdur Rahman Crescent Institute of Science and Technology, Vandalur, Chennai, Tamil Nadu, 600048, India.
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Dembicka-Mączka D, Kępa M, Fiegler-Rudol J, Grzech-Leśniak Z, Matys J, Grzech-Leśniak K, Wiench R. Evaluation of the Disinfection Efficacy of Er: YAG Laser Light on Single-Species Candida Biofilms-An In Vitro Study. Dent J (Basel) 2025; 13:88. [PMID: 39996962 PMCID: PMC11853755 DOI: 10.3390/dj13020088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Revised: 02/13/2025] [Accepted: 02/17/2025] [Indexed: 02/26/2025] Open
Abstract
Background/Objectives: Oral candidiasis is an opportunistic infection caused by Candida species. Recently, antifungal drugs have become less effective due to yeast resistance, emphasizing the need for new treatment strategies. This study aimed to assess the effect of the Er:YAG laser on the inhibition of growth and elimination of mature single-species Candida biofilms. Methods: The study utilized reference strains of C. albicans, C. glabrata, C. parapsilosis, and C. krusei organized in single-species biofilms on Sabouraud dextrose agar (SDA). First part: Candida suspensions (0.5 McFarland standard) were spread on SDA plates-two for each strain. Er:YAG laser irradiation was applied in a single pulse mode, 30 to 400 mJ, to 32 predetermined points. The growth inhibition zones (GIZs) were measured at 24-96 h of incubation. Second part: biofilms were prepared similarly and, after 96 h of incubation, exposed to Er:YAG laser irradiation at different energies (50, 100, 150, 200 mJ) for 180 s, per 1.44 cm area. Post-irradiation, impressions were taken using Rodac Agar to determine yeast counts. The count of colony-forming units (CFU) after irradiation was measured and results were analysed statistically. Results: First part: GIZ was found in all irradiated sites, with various Candida strains. The results showed a significant increase in the width of GIZ in the energy range of 30-280 mJ and a non-significant increase in the energy range of 300-400 mJ. Second part: the number of CFU remaining after the irradiation of biofilms with 150 mJ energy differed statistically significantly from other results obtained after using 50, 100, or 200 mJ energy, regardless of the Candida strain tested. Conclusions: The Er:YAG is shown to have good disinfecting properties (inhibiting biofilm growth, even at low-energy doses (50 mJ), and eliminating maturity, Candida spp. biofilms most effective on the 150 mJ energy dose).
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Affiliation(s)
- Diana Dembicka-Mączka
- EMDOLA Student, Department of Periodontal and Oral Mucosa Diseases, Wroclaw Medical University, 50-425 Wroclaw, Poland;
| | - Małgorzata Kępa
- Department of Microbiology, Faculty of Pharmaceutical Sciences in Sosnowiec, Silesian Medical University, 41-902 Katowice, Poland;
| | - Jakub Fiegler-Rudol
- Department of Periodontal and Oral Mucosa Diseases, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland;
| | | | - Jacek Matys
- Dental Surgery Department, Wroclaw Medical University, 50-425 Wroclaw, Poland;
| | - Kinga Grzech-Leśniak
- Dental Surgery Department, Wroclaw Medical University, 50-425 Wroclaw, Poland;
- Department of Periodontics, School of Dentistry, Virginia Commonwealth University, Richmond, VA 23284, USA
| | - Rafał Wiench
- Department of Periodontal and Oral Mucosa Diseases, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland;
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40
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Fin MT, dos Santos KS, Gualque MWDL, dos Santos RC, Aoki NCM, Auler ME, Fusco-Almeida AM, Mendes-Gianinni MJS, Mainardes RM. Development, Safety, and Therapeutic Evaluation of Voriconazole-Loaded Zein-Pectin-Hyaluronic Acid Nanoparticles Using Alternative In Vivo Models for Efficacy and Toxicity. Pharmaceutics 2025; 17:231. [PMID: 40006598 PMCID: PMC11859033 DOI: 10.3390/pharmaceutics17020231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Revised: 01/30/2025] [Accepted: 02/06/2025] [Indexed: 02/27/2025] Open
Abstract
Background/Objectives: Fungal infections caused by Candida species remain a significant clinical challenge, exacerbated by limitations in current antifungal therapies, including toxicity and poor bioavailability. This study aimed to develop and evaluate voriconazole-loaded zein-pectin-hyaluronic acid nanoparticles (ZPHA-VRC NPs) as a novel drug delivery system to enhance efficacy and reduce toxicity. Alternative in vitro and in vivo models were utilized to assess the safety and therapeutic potential of the nanoparticles. Methods: ZPHA-VRC NPs were prepared using a nanoprecipitation method and characterized for particle size, polydispersity index, zeta potential, and encapsulation efficiency. Antifungal activity was assessed via MIC assays against Candida albicans, C. krusei, and C. parapsilosis. Cytotoxicity was evaluated on Vero cells, while in vivo toxicity and efficacy were assessed using Galleria mellonella and Caenorhabditis elegans models. The therapeutic efficacy was further evaluated in an infected Caenorhabditis elegans model using survival and health scores. Results: ZPHA-VRC nanoparticles exhibited favorable physicochemical properties, including a particle size of approximately 192 nm, a polydispersity index of 0.079, a zeta potential of -24 mV, and an encapsulation efficiency of 34%. The nanoparticles retained antifungal activity comparable to free voriconazole while significantly reducing cytotoxicity. In vivo studies using G. mellonella and C. elegans demonstrated that ZPHA-VRC NPs markedly improved survival rates, reduced fungal burden, and enhanced health scores in infected models, outperforming the free drug. Additionally, the nanoparticles exhibited a superior safety profile, minimizing systemic toxicity while maintaining therapeutic efficacy. Conclusions: ZPHA-VRC NPs offer a safer and more effective delivery system for VRC, addressing the limitations of conventional formulations. The integration of alternative efficacy and safety models highlights their value in preclinical research.
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Affiliation(s)
- Margani Taise Fin
- Laboratory of Nanostructured Formulations, Universidade Estadual do Centro-Oeste (UNICENTRO), Alameda Élio Antônio Dalla Vecchia, 838, Guarapuava 85040-167, PR, Brazil;
| | - Kelvin Sousa dos Santos
- Department of Clinical Analysis, School of Pharmaceutical Sciences, Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Rodovia Araraquara Jaú, Km 01, Araraquara 14801-902, SP, Brazil; (K.S.d.S.); (M.W.d.L.G.); (R.C.d.S.); (N.C.M.A.); (A.M.F.-A.); (M.J.S.M.-G.)
| | - Marcos William de Lima Gualque
- Department of Clinical Analysis, School of Pharmaceutical Sciences, Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Rodovia Araraquara Jaú, Km 01, Araraquara 14801-902, SP, Brazil; (K.S.d.S.); (M.W.d.L.G.); (R.C.d.S.); (N.C.M.A.); (A.M.F.-A.); (M.J.S.M.-G.)
| | - Rafaela Cristine dos Santos
- Department of Clinical Analysis, School of Pharmaceutical Sciences, Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Rodovia Araraquara Jaú, Km 01, Araraquara 14801-902, SP, Brazil; (K.S.d.S.); (M.W.d.L.G.); (R.C.d.S.); (N.C.M.A.); (A.M.F.-A.); (M.J.S.M.-G.)
| | - Natália Cristina Morici Aoki
- Department of Clinical Analysis, School of Pharmaceutical Sciences, Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Rodovia Araraquara Jaú, Km 01, Araraquara 14801-902, SP, Brazil; (K.S.d.S.); (M.W.d.L.G.); (R.C.d.S.); (N.C.M.A.); (A.M.F.-A.); (M.J.S.M.-G.)
| | - Marcos Ereno Auler
- Pharmacy Department, Universidade Estadual do Centro-Oeste (UNICENTRO), Alameda Élio Antônio Dalla Vecchia, 838, Guarapuava 85040-167, PR, Brazil;
| | - Ana Marisa Fusco-Almeida
- Department of Clinical Analysis, School of Pharmaceutical Sciences, Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Rodovia Araraquara Jaú, Km 01, Araraquara 14801-902, SP, Brazil; (K.S.d.S.); (M.W.d.L.G.); (R.C.d.S.); (N.C.M.A.); (A.M.F.-A.); (M.J.S.M.-G.)
| | - Maria José Soares Mendes-Gianinni
- Department of Clinical Analysis, School of Pharmaceutical Sciences, Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Rodovia Araraquara Jaú, Km 01, Araraquara 14801-902, SP, Brazil; (K.S.d.S.); (M.W.d.L.G.); (R.C.d.S.); (N.C.M.A.); (A.M.F.-A.); (M.J.S.M.-G.)
| | - Rubiana Mara Mainardes
- Laboratory of Nanostructured Formulations, Universidade Estadual do Centro-Oeste (UNICENTRO), Alameda Élio Antônio Dalla Vecchia, 838, Guarapuava 85040-167, PR, Brazil;
- Pharmacy Department, Universidade Estadual do Centro-Oeste (UNICENTRO), Alameda Élio Antônio Dalla Vecchia, 838, Guarapuava 85040-167, PR, Brazil;
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Gomez-Artiguez L, de la Cámara-Fuentes S, Sun Z, Hernáez ML, Borrajo A, Pitarch A, Molero G, Monteoliva L, Moritz RL, Deutsch EW, Gil C. Candida albicans: a comprehensive view of the proteome. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2024.12.20.629377. [PMID: 39763837 PMCID: PMC11702768 DOI: 10.1101/2024.12.20.629377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/15/2025]
Abstract
We describe a new release of the Candida albicans PeptideAtlas proteomics spectral resource (build 2024-03), providing a sequence coverage of 79.5% at the canonical protein level, matched mass spectrometry spectra, and experimental evidence identifying 3382 and 536 phosphorylated serine and threonine sites with false localization rates of 1% and 5.3%, respectively. We provide a tutorial on how to use the PeptideAtlas and associated tools to access this information. The C. albicans PeptideAtlas summary web page provides "Build overview", "PTM coverage", "Experiment contribution", and "Dataset contribution" information. The protein and peptide information can also be accessed via the Candida Genome Database via hyperlinks on each protein page. This allows users to peruse identified peptides, protein coverage, post-translational modifications (PTMs), and experiments identifying each protein. Given the value of understanding the PTM landscape in the sequence of each protein, a more detailed explanation of how to interpret and analyse PTM results is provided in the PeptideAtlas of this important pathogen. Candida albicans PeptideAtlas web page: https://db.systemsbiology.net/sbeams/cgi/PeptideAtlas/buildDetails?atlas_build_id=578.
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Affiliation(s)
- Leticia Gomez-Artiguez
- Microbiology and Parasitology Department, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid
| | | | - Zhi Sun
- Institute for Systems Biology, 401 Terry Ave North, Seattle, WA, USA. 98109
| | - María Luisa Hernáez
- Proteomics Unit, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid
| | - Ana Borrajo
- Microbiology and Parasitology Department, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid
| | - Aída Pitarch
- Microbiology and Parasitology Department, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid
| | - Gloria Molero
- Microbiology and Parasitology Department, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid
| | - Lucía Monteoliva
- Microbiology and Parasitology Department, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid
| | - Robert L. Moritz
- Institute for Systems Biology, 401 Terry Ave North, Seattle, WA, USA. 98109
| | - Eric W. Deutsch
- Institute for Systems Biology, 401 Terry Ave North, Seattle, WA, USA. 98109
| | - Concha Gil
- Microbiology and Parasitology Department, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid
- Proteomics Unit, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid
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42
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Thu Le H, Luc Phuong TT, Huy GH, Nguyen PV, Nguyen BVG. Investigation of the optimal condition for the growth and biofilm development of Candida albicans on three dental materials. IRANIAN JOURNAL OF MICROBIOLOGY 2025; 17:153-162. [PMID: 40330050 PMCID: PMC12049753 DOI: 10.18502/ijm.v17i1.17813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/08/2025]
Abstract
Background and Objectives Candida albicans as pathogenic fungi cause conditions like oral candidiasis and dental caries. The critical role of biofilms in the pathogenicity of C. albicans necessitates the exploration of conditions that promote their growth and development. Our study aimed to delineate the optimal conditions conducive to the proliferation and biofilm production of C. albicans on prevalent dental materials. Materials and Methods To approximate oral cavity conditions, culture media were enhanced with various glucose concentrations to assess the growth and biofilm-forming capability of the fungus through growth curve analysis and crystal violet assays. Results The findings suggest that YPG medium augmented with 4% glucose presents as an optimal environment for C. albicans growth. Biofilm formation was most effectively promoted in RPMI medium supplemented with the same concentration of glucose. Composite resin was identified as the substrate most susceptible to biofilm development by C. albicans under these conditions. Conclusion This investigation highlights the necessity of accounting for microbial activity and material characteristics in the prevention and management of dental biofilm formation. Our research advances the understanding of in vitro cultivation of C. albicans, simulating the oral milieu more accurately and contributing to enhanced oral health management for individuals utilizing temporary dental fixtures.
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Affiliation(s)
- Hoai Thu Le
- Center of Molecular Biomedicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Truong Thi Luc Phuong
- Faculty of Odonto – Stomatology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Giang Hoang Huy
- Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Phuoc-Vinh Nguyen
- Faculty of Pharmacy, University of Health Sciences, Vietnam National University Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Bac Vu Giang Nguyen
- Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
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43
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de Souza ÁL, da Silva Campelo M, de Sousa Mesquita G, Nobre AFD, de Freitas Franco VM, Barreto ACH, de Sousa JS, Honório Júnior JER, Brilhante RSN, Ricardo NMPS, de Aguiar Soares S, Ribeiro MENP. Influence of Agaricus blazei Murill polysaccharides on synthesis, stabilization, acute toxicity and antifungal activity of copper (II) oxide nanoparticles. Biometals 2025; 38:231-244. [PMID: 39572476 DOI: 10.1007/s10534-024-00650-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Accepted: 11/02/2024] [Indexed: 01/03/2025]
Abstract
In general, nanomaterials tend to have better physical, chemical and biological properties than conventional materials. Furthermore, the polysaccharides from Agaricus blazei Murill mushroom have several pharmacological properties, in addition to low cytotoxicity and high biocompatibility. This work sought to merge the properties of CuO nanoparticles and Agaricus blazei Murill polysaccharides through syntheses and coatings with the aim of evaluating their toxicity in adult zebrafish and antifungal activity against C. albicans and C. parapsilosis. The nanoparticles were synthesized using the coprecipitation method and subsequently characterized in terms of their physicochemical properties using spectroscopic and thermoanalytical techniques. Furthermore, their composition was determined by X-Ray Diffraction and their morphology was studied using different microscopic techniques. CuO nanoparticles coated with Agaricus blazei Murill polysaccharides showed smaller particle size. Dispersions of nanoparticles coated with the polysaccharides were found to be more stable than their uncoated counterparts. The nanoparticles also showed antifungal activity against Candida sp. strains, with MIC50 values between 64 and 512 µg mL-1. It was observed that coating the materials with polysaccharides preserved their antifungal properties and reduced acute toxicity against adult zebrafish. Therefore, it is estimated that the CuO nanoparticles coated with Agaricus blazei Murill polysaccharides are innovative nanomaterials with potential for future clinical applications, especially in the topical treatment of candidiasis.
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Affiliation(s)
- Álamo Lourenço de Souza
- Department of Organic and Inorganic Chemistry, Polymers and Materials Innovation Laboratory, Federal University of Ceara, Pici Campus, Fortaleza, CE, 60440-900, Brazil
| | - Matheus da Silva Campelo
- Department of Organic and Inorganic Chemistry, Polymers and Materials Innovation Laboratory, Federal University of Ceara, Pici Campus, Fortaleza, CE, 60440-900, Brazil
| | - Gabriel de Sousa Mesquita
- Department of Organic and Inorganic Chemistry, Polymers and Materials Innovation Laboratory, Federal University of Ceara, Pici Campus, Fortaleza, CE, 60440-900, Brazil
| | - Augusto Feynman Dias Nobre
- Department of Pathology and Legal Medicine, School of Medicine, Specialized Medical Mycology Center, Federal University of Ceará, Porangabuçu Campus, Fortaleza, CE, 60425-540, Brazil
| | | | | | - Jeanlex Soares de Sousa
- Department of Physics, Federal University of Ceara, Pici Campus, Fortaleza, CE, 60455-970, Brazil
| | | | - Raimunda Sâmia Nogueira Brilhante
- Department of Pathology and Legal Medicine, School of Medicine, Specialized Medical Mycology Center, Federal University of Ceará, Porangabuçu Campus, Fortaleza, CE, 60425-540, Brazil
| | - Nágila Maria Pontes Silva Ricardo
- Department of Organic and Inorganic Chemistry, Polymers and Materials Innovation Laboratory, Federal University of Ceara, Pici Campus, Fortaleza, CE, 60440-900, Brazil
| | - Sandra de Aguiar Soares
- Department of Organic and Inorganic Chemistry, Polymers and Materials Innovation Laboratory, Federal University of Ceara, Pici Campus, Fortaleza, CE, 60440-900, Brazil.
| | - Maria Elenir Nobre Pinho Ribeiro
- Department of Organic and Inorganic Chemistry, Polymers and Materials Innovation Laboratory, Federal University of Ceara, Pici Campus, Fortaleza, CE, 60440-900, Brazil.
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44
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Garg M, Verma M, Khan AS, Yadav P, Rahman SS, Ali A, Kamthan M. Cadmium-induced augmentation of fungal translocation promotes systemic infection in mice via gut barrier disruption and immune dysfunction. Life Sci 2025; 362:123368. [PMID: 39756275 DOI: 10.1016/j.lfs.2025.123368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 12/27/2024] [Accepted: 01/01/2025] [Indexed: 01/07/2025]
Abstract
Cadmium (Cd) disrupts the immune system and intestinal barrier, increasing infection risk and gut dysbiosis. Its impact on intestinal fungi, particularly the opportunistic pathogen Candida albicans, which can cause systemic infections in immunocompromised patients, is not well understood. Our study revealed that C. albicans exhibited high tolerance and maintained its morphogenetic switching in response to Cd. As C. albicans is not naturally found in the mouse gut, we attempted intestinal colonization of C. albicans-SC5314 strain using standard procedures. However, the intestinal fungal load decreased and was undetectable by 15th day. To assess the effects of sub-chronic Cd exposure, both oral and intravenous methods were used. Oral exposure to C. albicans (105 CFU/ml) resulted in a 10-fold increase in intestinal translocation in Cd-exposed mice (0.98 mg/kg) compared to controls. Cd exposure also downregulated intestinal tight junction proteins and increased FITC-dextran permeability, indicating that Cd disrupts the intestinal barrier and facilitates C. albicans translocation. Moreover, Cd-exposed mice showed significant morbidity and higher fungal loads in organs after intravenous non-lethal dose of C. albicans, along with a subdued cytokine response. These findings highlight the significant impact of Cd on fungal pathogenicity and immune response, pointing to the broader health risks of Cd exposure.
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Affiliation(s)
- Manika Garg
- Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India
| | - Muskan Verma
- Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India
| | - Aiysha Siddiq Khan
- Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India
| | - Pawan Yadav
- Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India
| | - Saman Saim Rahman
- Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India
| | - Asghar Ali
- Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India
| | - Mohan Kamthan
- Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India.
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45
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Tajane SB, Pawar S, Patil S. Revisiting the History of Candidiasis. Cureus 2025; 17:e78878. [PMID: 40091922 PMCID: PMC11909613 DOI: 10.7759/cureus.78878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Accepted: 02/11/2025] [Indexed: 03/19/2025] Open
Abstract
Candida infections in humans are well-documented, but their clinical manifestations have become more evident in recent years. This shift is attributed to advancements in diagnostic modalities and the increasing use of aggressive therapies, where patients are exposed to more invasive procedures, broad-spectrum antibiotics, and immunosuppressive drugs. This shift is attributed to advancements in diagnostic modalities and the increasing use of aggressive therapies, where patients are exposed to more invasive procedures, broad-spectrum antibiotics, and immunosuppressive drugs. This review article outlines various historical milestones regarding multiple aspects of Candida, including its taxonomy, epidemiology, pathogenicity, and therapeutic and diagnostic modalities. A thorough search of the available literature was conducted using scientific search engines such as Google Scholar, PubMed, and ScienceDirect, utilizing appropriate Medical Subject Headings terms. Relevant research articles highlighting important historical milestones related to Candida's taxonomy, pathogenicity, clinical manifestations, diagnostic modalities, and treatment were retrieved and utilized to prepare this manuscript. The historical perspective of Candida is dynamic, and while many aspects have become clear over the years, there are still numerous areas that need further elucidation to fully understand the complex mechanisms of pathogenicity, epidemiology, and antifungal resistance. Additionally, this review aims to provide new insights that will support the development of novel antifungal molecules to expand the current antifungal armamentarium against Candida, which, at present, is limited to three classes: azoles, polyenes, and echinocandins.
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Affiliation(s)
- Savita B Tajane
- Department of Microbiology, Krishna Institute of Medical Sciences, Krishna Vishwa Vidyapeeth, Karad, IND
| | - Satyajeet Pawar
- Department of Microbiology, Krishna Institute of Medical Sciences, Krishna Vishwa Vidyapeeth, Karad, IND
| | - Satish Patil
- Department of Microbiology, Krishna Institute of Medical Sciences, Krishna Vishwa Vidyapeeth, Karad, IND
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van Thiel IAM, Kreulen IAM, Bénard MV, de Goffau MC, Theelen B, Heinsbroek SEM, Zylka PK, Ponsioen CY, Boekhout T, de Jonge WJ, Rosendahl S, van den Wijngaard RM, Hagen F. Typing of feces-derived Candida albicans strains using a novel seven-locus microsatellite panel reveals associations with yeast phenotype in individuals with inflammatory bowel disease. Pathog Dis 2025; 83:ftaf001. [PMID: 39794285 PMCID: PMC11781193 DOI: 10.1093/femspd/ftaf001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 11/14/2024] [Accepted: 01/09/2025] [Indexed: 01/13/2025] Open
Abstract
Inflammatory diseases of the human gastrointestinal tract are affected by the microbes that reside in the mucosal surfaces. Patients with inflammatory bowel diseases (IBD) have altered bacterial and fungal intestinal compositions, including higher levels of fecal Candida yeasts. Ongoing research indicates that genetic and phenotypic diversity of Candida albicans may be linked with disease severity. Here, we set out to investigate feces-derived C. albicans strains from individuals with IBD and healthy volunteers through microsatellite-based genotyping and phenotypic assays. A seven-locus microsatellite panel was applied, of which six loci were newly developed. It appears that there is no specific lineage of C. albicans that is associated with IBD, but rather that the three study populations (Crohn's disease, ulcerative colitis, healthy volunteers) do have distinguishable distributions of genotypes. In addition, phenotypic characterization by means of enzyme release assays revealed trends between genotypes, virulence-related enzyme activity, and clinical biomarkers. We thus show that microsatellite typing can describe genetic diversity of feces-derived C. albicans strains, and that phenotypic diversity of these strains may indeed correlate with fungal genotype or disease. This study opens further possibilities to investigate fecal fungi in relation to severity of inflammation in IBD or in other (intestinal) diseases.
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Affiliation(s)
- Isabelle A M van Thiel
- Westerdijk Fungal Biodiversity Institute, Royal Dutch Academy of Arts and Sciences, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
- Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, Location Academic Medical Center (AMC), Meibergdreef 69-71, 1105 BK Amsterdam, The Netherlands
- Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Irini A M Kreulen
- Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, Location Academic Medical Center (AMC), Meibergdreef 69-71, 1105 BK Amsterdam, The Netherlands
- Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Mèlanie V Bénard
- Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Location Academic Medical Center (AMC). Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Marcus C de Goffau
- Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, Location Academic Medical Center (AMC), Meibergdreef 69-71, 1105 BK Amsterdam, The Netherlands
- Wellcome Sanger Institute, Hinxton, Saffron Walden CB10 1RQ, United Kingdom
| | - Bart Theelen
- Westerdijk Fungal Biodiversity Institute, Royal Dutch Academy of Arts and Sciences, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
| | - Sigrid E M Heinsbroek
- Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, Location Academic Medical Center (AMC), Meibergdreef 69-71, 1105 BK Amsterdam, The Netherlands
- Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Location Academic Medical Center (AMC). Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Patrycja K Zylka
- Westerdijk Fungal Biodiversity Institute, Royal Dutch Academy of Arts and Sciences, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
| | - Cyriel Y Ponsioen
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Location Academic Medical Center (AMC). Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Teun Boekhout
- Westerdijk Fungal Biodiversity Institute, Royal Dutch Academy of Arts and Sciences, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
| | - Wouter J de Jonge
- Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, Location Academic Medical Center (AMC), Meibergdreef 69-71, 1105 BK Amsterdam, The Netherlands
- Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Location Academic Medical Center (AMC). Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
- Department of General, Visceral, Thoracic and Vascular Surgery, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
| | - Søren Rosendahl
- Department of Biology, University of Copenhagen, Universitetsparken 15, DK-2100 Copenhagen, Denmark
| | - René M van den Wijngaard
- Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, Location Academic Medical Center (AMC), Meibergdreef 69-71, 1105 BK Amsterdam, The Netherlands
- Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Location Academic Medical Center (AMC). Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Ferry Hagen
- Westerdijk Fungal Biodiversity Institute, Royal Dutch Academy of Arts and Sciences, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
- Institute for Biodiversity and Ecosystem Dynamics (IBED), University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands
- Department of Medical Microbiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
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Ouzounthanasis KA, Glamočlija J, Ćirić A, Koumbis AE. Studies of the Synthesis of Fused Isoxazoline/Isoquinolinones and Evaluation of the Antifungal Activity of Isoxazole-like Benzamide and Isoquinolinone Hybrids. Molecules 2025; 30:589. [PMID: 39942692 DOI: 10.3390/molecules30030589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2024] [Revised: 01/26/2025] [Accepted: 01/26/2025] [Indexed: 05/09/2025] Open
Abstract
Isoxazole derivatives (isoxazoles, isoxazolines, and isoxazolidines) are present in the structure of several natural products and/or pharmaceutically interesting compounds. In this work, a synthetic study for the preparation of fused isoxazoline/isoquinolinone hybrids is presented. The initial approach involving the sequential 1,3-dipolar cycloaddition of nitrile oxides to indenone (to obtain the isoxazoline ring) and a Beckmann rearrangement (to construct the isoquinolinone lactam system) was complicated by the formation of fragmentation products during the latter. Therefore, the desired hybrids were successfully reached by applying DDQ-mediated oxidation of the respective isoxazolidines. Based on the results, key observations were made regarding the mechanism of the Beckmann reaction. Moreover, selected isoxazole benzamides and fused isoxazoline/isoxazolidine isoquinolinones were in vitro evaluated against a series of fungi strains (including a 2D checkerboard assay with ketoconazole), revealing that some of these compounds exhibit promising antifungal activity.
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Affiliation(s)
- Konstantinos A Ouzounthanasis
- Laboratory of Organic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - Jasmina Glamočlija
- Department of Plant Physiology, Institute for Biological Research "Siniša Stanković"-National Institute of Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia
| | - Ana Ćirić
- Department of Plant Physiology, Institute for Biological Research "Siniša Stanković"-National Institute of Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia
| | - Alexandros E Koumbis
- Laboratory of Organic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
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48
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Goh E, Chavatte JM, Lin RTP, Ng LFP, Rénia L, Oon HH. Vaccines in Dermatology-Present and Future: A Review. Vaccines (Basel) 2025; 13:125. [PMID: 40006672 PMCID: PMC11860801 DOI: 10.3390/vaccines13020125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 01/16/2025] [Accepted: 01/18/2025] [Indexed: 02/27/2025] Open
Abstract
Dermatological vaccines have emerged as critical tools in preventing and managing a wide spectrum of skin conditions ranging from infectious diseases to malignancies. By synthesizing evidence from existing literature, this review aims to comprehensively evaluate the efficacy, safety, and immunogenicity of vaccines used in dermatology, including both approved vaccines and those currently being researched. Vaccines discussed in this paper include those targeting dermatoses and malignancies (e.g., acne vulgaris, atopic dermatitis, and melanoma); infectious diseases (e.g., human papillomavirus (HPV); varicella zoster virus (VZV); herpes zoster (HZ); warts; smallpox; mpox (monkeypox); hand, foot, and mouth disease (HFMD); candidiasis and Group B Streptococcus (GBS); and neglected tropical diseases (e.g., Buruli ulcer, leprosy, and leishmaniasis). Through this review, we aim to provide a detailed understanding of the role of vaccines in dermatology, identify knowledge gaps, and propose areas for future research.
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Affiliation(s)
- Eyan Goh
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore; (E.G.); (L.F.P.N.); (L.R.)
| | - Jean-Marc Chavatte
- National Public Health Laboratory, Singapore 308442, Singapore; (J.-M.C.); (R.T.P.L.)
| | - Raymond T. P. Lin
- National Public Health Laboratory, Singapore 308442, Singapore; (J.-M.C.); (R.T.P.L.)
- National University Hospital Singapore, Singapore 119077, Singapore
| | - Lisa F. P. Ng
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore; (E.G.); (L.F.P.N.); (L.R.)
- A*STAR Infectious Diseases Labs (A*STAR IDL), Agency for Science, Technology, and Research (A*STAR), Singapore 138648, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
| | - Laurent Rénia
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore; (E.G.); (L.F.P.N.); (L.R.)
- A*STAR Infectious Diseases Labs (A*STAR IDL), Agency for Science, Technology, and Research (A*STAR), Singapore 138648, Singapore
- School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore
| | - Hazel H. Oon
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore; (E.G.); (L.F.P.N.); (L.R.)
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
- National Skin Centre and Skin Research Institute of Singapore, Singapore 308205, Singapore
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Gaffar NR, Valand N, Venkatraman Girija U. Candidiasis: Insights into Virulence Factors, Complement Evasion and Antifungal Drug Resistance. Microorganisms 2025; 13:272. [PMID: 40005639 PMCID: PMC11858274 DOI: 10.3390/microorganisms13020272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/23/2025] [Accepted: 01/24/2025] [Indexed: 02/27/2025] Open
Abstract
Invasive fungal infections constitute a substantial global health burden, with invasive candidiasis representing approximately 70% of reported cases worldwide. The emergence of antifungal resistance among Candida species has further exacerbated this challenge to healthcare systems. Recent epidemiological studies have documented a concerning shift towards non-albicans Candida species, exhibiting reduced antifungal susceptibility, in invasive candidiasis cases. The complement system serves as a crucial first-line defence mechanism against Candida infections. These fungal pathogens can activate the complement cascade through three conventional pathways-classical, lectin, and alternative-in addition to activation through the coagulation system. While these pathways are initiated by distinct molecular triggers, they converge at C3 convertase formation, ultimately generating biologically active products and the membrane attack complex. Candida species have evolved sophisticated mechanisms to evade complement-mediated host defence, including the masking of cell wall components, proteolytic cleavage and inhibition of complement proteins, recruitment of complement regulators, and acquisition of host proteins. This review examines the intricate interplay between Candida species and the host complement system, with emphasis on complement evasion strategies. Furthermore, we highlight the importance of exploring the crosstalk between antifungal resistance and immune evasion strategies employed by Candida species. Understanding these interactions may facilitate the development of novel therapeutic approaches and strategies to overcome treatment failures in Candida species infections.
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Affiliation(s)
| | | | - Umakhanth Venkatraman Girija
- Leicester School of Allied Health Sciences, Faculty of Health & Life Sciences, De Montfort University, Leicester LE1 9BH, UK
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Zhang M, Yang W, Liu N, Tu J, Lin J, Dong G, Zhao D, Sheng C. Lanosterol 14α-Demethylase (CYP51)/Heat Shock Protein 90 (Hsp90) Dual Inhibitors for the Treatment of Invasive Candidiasis. J Med Chem 2025; 68:1668-1681. [PMID: 39754582 DOI: 10.1021/acs.jmedchem.4c02305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
Invasive candidiasis has attracted global attention with a high incidence and mortality. Current antifungal drugs are limited by unfavorable therapeutic efficacy, significant hepatorenal toxicity, and the development of drug resistance. Herein, we designed the first generation of lanosterol 14α-demethylase (CYP51)/heat shock protein 90 (Hsp90) dual inhibitors on the basis of antifungal synergism. Among them, dual inhibitor MM4 exhibited potent in vitro and in vivo antifungal activity against Candida albicans and effectively inhibited important fungal virulence factors (e.g., hyphae, biofilm). Therefore, CYP51/Hsp90 dual inhibitors show great promise in the development of novel antifungal drugs to combat invasive candidiasis.
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Affiliation(s)
- Mingming Zhang
- The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China
| | - Wanzhen Yang
- The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China
| | - Na Liu
- The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China
| | - Jie Tu
- The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China
| | - Jingsheng Lin
- Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China
| | - Guoqiang Dong
- The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China
| | - Dongmei Zhao
- Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China
| | - Chunquan Sheng
- The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China
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