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Bhargava A, Klamer K, Sharma M, Ortiz D, Saravolatz L. Candida auris: A Continuing Threat. Microorganisms 2025; 13:652. [PMID: 40142543 PMCID: PMC11946832 DOI: 10.3390/microorganisms13030652] [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: 02/01/2025] [Revised: 03/05/2025] [Accepted: 03/07/2025] [Indexed: 03/28/2025] Open
Abstract
Candida auris is a World Health Organization critical-priority fungal pathogen that has variable resistance to antifungal treatments. Multiple clades have been identified through genomic analysis and have appeared in different geographic locations simultaneously. Due to a combination of factors including antifungal resistance, ability to colonize and persist in the environment, and thermotolerance, it can thrive. Infected patients are associated with a high mortality rate, especially those with multiple health risk factors like those associated with other Candida species. This review highlights the current situation of this pathogen to help provide guidance for future work.
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Affiliation(s)
- Ashish Bhargava
- Thomas Mackey Center of Infectious Diseases, Henry Ford Health—St. John Hospital, Detroit, MI 48236, USA
- School of Medicine, Wayne State University, Detroit, MI 48202, USA
| | - Katherine Klamer
- Thomas Mackey Center of Infectious Diseases, Henry Ford Health—St. John Hospital, Detroit, MI 48236, USA
| | - Mamta Sharma
- Thomas Mackey Center of Infectious Diseases, Henry Ford Health—St. John Hospital, Detroit, MI 48236, USA
| | - Daniel Ortiz
- LabCorp—Health Systems Operating Division, Troy, MI 48083, USA
| | - Louis Saravolatz
- Thomas Mackey Center of Infectious Diseases, Henry Ford Health—St. John Hospital, Detroit, MI 48236, USA
- School of Medicine, Wayne State University, Detroit, MI 48202, USA
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Coutinho TDNP, Rodrigues FAM, de Assis DA, Rebouças LM, Ferreira TL, Cabral VPDF, Rodrigues DS, Sá LGDAV, Lopes FFDS, do Nascimento GA, Mattos ALA, Cavalcanti BC, Júnior HVN, da Silva CR, Ricardo NMPS. Microspheres based on galactomannan and Spondias purpurea L. extract to increase antifungal and antibiofilm efficacy against Candida spp. Int J Biol Macromol 2025; 297:139788. [PMID: 39805454 DOI: 10.1016/j.ijbiomac.2025.139788] [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: 09/10/2024] [Revised: 12/29/2024] [Accepted: 01/10/2025] [Indexed: 01/16/2025]
Abstract
The ongoing problem of an increasing resistance of Candida spp. to available antifungals, has made it necessary the search for new therapeutic alternatives. The aim of this work was to develop a microsphere based on Caesalpinia ferrea galactomannan and Spondias purpurea L. stem bark extract using the spray drying technique and evaluate its antimicrobial effect on biofilm formation and planktonic cells of Candida spp. Differential scanning calorimetry (DSC), infrared analysis (IR) and scanning electron microscopy (SEM) were used to characterize the microsphere, in addition to the encapsulation efficiency by HPLC to quantify the extract in the microsphere. In microbiological analyses, broth microdilution and antibiofilm tests were carried out. The results of the minimum inhibitory concentration (MIC) for the stem bark extract (SBE) were within 0.5-2 μg mL-1 and the galactomannan microsphere (GMB) 1-8 μg mL-1. As for the biofilm, the microsphere compared to the extract showed a statistically significant improvement at 8xMIC for C. albicans 1, while for C. auris, it was at 4xMIC and 8xMIC. Furthermore, SBE and GMB did not present toxicity. The study revealed that the synthesized microspheres have the potential to be used as an antifungal agent.
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Affiliation(s)
- Tatiana do N P Coutinho
- Laboratory of Polymers and Materials Innovation, Department of Organic and Inorganic Chemistry, Sciences Center, Federal University of Ceará, Campus of Pici, Zip Code 60440-900 Fortaleza, CE, Brazil; Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, Brazil; Center for Research and Development of Medicines, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Francisco A M Rodrigues
- Laboratory of Polymers and Materials Innovation, Department of Organic and Inorganic Chemistry, Sciences Center, Federal University of Ceará, Campus of Pici, Zip Code 60440-900 Fortaleza, CE, Brazil
| | - David A de Assis
- Laboratory of Polymers and Materials Innovation, Department of Organic and Inorganic Chemistry, Sciences Center, Federal University of Ceará, Campus of Pici, Zip Code 60440-900 Fortaleza, CE, Brazil.
| | - Louhana M Rebouças
- Laboratory of Polymers and Materials Innovation, Department of Organic and Inorganic Chemistry, Sciences Center, Federal University of Ceará, Campus of Pici, Zip Code 60440-900 Fortaleza, CE, Brazil; Federal Institute of Education, Science and Technology of Ceará, Fortaleza, CE 60410-426, Brazil
| | - Thais L Ferreira
- Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, Brazil; Center for Research and Development of Medicines, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Vitória P de F Cabral
- Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, Brazil; Center for Research and Development of Medicines, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Daniel S Rodrigues
- Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, Brazil; Center for Research and Development of Medicines, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Lívia G do A V Sá
- Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, Brazil; Center for Research and Development of Medicines, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Francisco F da S Lopes
- Laboratory of Chemistry of Natural Products, Postgraduate Program in Biotechnology, Ceará State University, Itaperi Campus s/N° CEP, 60714/903 Fortaleza, Ceará, Brazil
| | - Gabriela A do Nascimento
- NutriFisher Study Group, Postgraduate Program in Nutrition and Health, State University of Ceará, Fortaleza 60714-903, CE, Brazil.
| | - Adriano L A Mattos
- Embrapa Tropical Agroindustry, Pici campus, Zip Code 60511-110 Fortaleza, CE, Brazil.
| | - Bruno C Cavalcanti
- Center for Research and Development of Medicines, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Hélio V N Júnior
- Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, Brazil; Center for Research and Development of Medicines, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Cecília R da Silva
- Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, Brazil; Center for Research and Development of Medicines, Federal University of Ceará, Fortaleza, Ceará, Brazil.
| | - Nágila M P S Ricardo
- Laboratory of Polymers and Materials Innovation, Department of Organic and Inorganic Chemistry, Sciences Center, Federal University of Ceará, Campus of Pici, Zip Code 60440-900 Fortaleza, CE, Brazil.
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Semenya MD, Aladejana AE, Ndlovu SI. Characterization of susceptibility patterns and adaptability of the newly emerged Candida auris. Int Microbiol 2025; 28:575-587. [PMID: 39107585 PMCID: PMC11906518 DOI: 10.1007/s10123-024-00563-1] [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: 05/01/2024] [Revised: 07/18/2024] [Accepted: 07/29/2024] [Indexed: 03/14/2025]
Abstract
The emergence of Candida auris has caused a major concern in the public health worldwide. This novel fungus is characterized by its multidrug resistance profile, ability to thrive in harsh and stressful conditions, as well as high temperatures and salt concentrations, persistence on hospital surfaces, causing nosocomial infections and outbreaks, and unique fitness properties. Here, we study the antifungal susceptibility patterns, thermotolerance, and halotolerance of 15 putative C. auris clinical isolates from Inkosi Albert Academic Hospital, Durban, South Africa. Five of the C. auris isolates showed resistance to all three antifungals (fluconazole, amphotericin B, and micafungin) and were selected for characterization of their adaptability mechanisms. Four of the tested multidrug-resistant C. auris isolates (C. auris strain F25, C. auris strain F276, C. auris F283, and C. auris M153) showed good growth when exposed to high temperature (42 °C) and salinity (10% NaCl) conditions whereas one isolate (C. auris F65) showed moderate growth under these conditions. Candida parapsilosis showed poor growth whereas C. albicans no growth under these conditions. The five C. auris strains were positive for all the adaptive features.
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Affiliation(s)
- Matlou D Semenya
- Department of Biotechnology and Food Technology, Faculty of Science, University of Johannesburg, Johannesburg, 2028, South Africa
| | - Adebowale E Aladejana
- Department of Biotechnology and Food Technology, Faculty of Science, University of Johannesburg, Johannesburg, 2028, South Africa
| | - Sizwe I Ndlovu
- Department of Biotechnology and Food Technology, Faculty of Science, University of Johannesburg, Johannesburg, 2028, South Africa.
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Wang LJ, Wang MJ, Jing L, Su R, Jian QJ, Zhang ZY, Xie ML. Impact of 222-nm ultraviolet disinfection combined with psychological care on the emotional and hospital infection of critical patients. World J Psychiatry 2025; 15:99449. [PMID: 39974489 PMCID: PMC11758054 DOI: 10.5498/wjp.v15.i2.99449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 11/26/2024] [Accepted: 12/19/2024] [Indexed: 01/14/2025] Open
Abstract
BACKGROUND Empathetic psychological care improves mood and enhances the quality of life in critically ill patients. AIM To study the impact of combining 222-nm ultraviolet (UV) disinfection with empathetic psychological care on emotional states, nosocomial infection rates, and quality of life in critically ill patients. METHODS A total of 202 critically ill patients admitted to Beijing Ditan Hospital (December 2023 to May 2024) were randomly assigned to control (Ctrl, n = 101) or observation groups (Obs, n = 101). The Ctrl group received 222-nm UV disinfection and routine care, while the Obs group received 222-nm UV disinfection with empathetic psychological care. Emotional states [Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS)], hospital infection rates, quality of life (36-Item Short Form Health Survey), and patient satisfaction were evaluated. RESULTS At baseline, there were no significant differences in SAS and SDS scores between the groups (P > 0.05). Following care, both groups demonstrated reductions in SAS and SDS scores, with the Obs group exhibiting a significantly greater reduction (P < 0.05). The Obs group also experienced a significantly lower overall hospital infection rate (P < 0.05). Similarly, while baseline 36-Item Short Form Health Survey scores did not differ significantly between the groups (P > 0.05), post-care scores improved in both groups, with a greater improvement observed in the Obs group (P < 0.05). Additionally, the Obs group reported higher patient satisfaction ratings (P < 0.05). CONCLUSION The combination of 222-nm UV disinfection and empathetic psychological care improves emotional states, reduces hospital infection rates, enhances the quality of life, and increases patient satisfaction among critically ill patients.
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Affiliation(s)
- Li-Juan Wang
- Department of Emergency, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Mei-Juan Wang
- Department of Emergency, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Lan Jing
- Department of Emergency, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Ran Su
- Department of Emergency, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Qiu-Ju Jian
- Department of Emergency, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Zhi-Yun Zhang
- Department of Nursing, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Mei-Lian Xie
- Department of Nursing, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
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Sartelli M, Marini CP, McNelis J, Coccolini F, Rizzo C, Labricciosa FM, Petrone P. Preventing and Controlling Healthcare-Associated Infections: The First Principle of Every Antimicrobial Stewardship Program in Hospital Settings. Antibiotics (Basel) 2024; 13:896. [PMID: 39335069 PMCID: PMC11428707 DOI: 10.3390/antibiotics13090896] [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: 08/13/2024] [Revised: 09/12/2024] [Accepted: 09/19/2024] [Indexed: 09/30/2024] Open
Abstract
Antimicrobial resistance (AMR) is one of the main public health global burdens of the 21st century, responsible for over a million deaths every year. Hospital programs aimed at improving antibiotic use, referred to as antimicrobial stewardship programs (ASPs), can both optimize the treatment of infections and minimize adverse antibiotics events including the development and spread of AMR. The challenge of AMR is closely linked to the development and spread of healthcare-associated infection (HAIs). In fact, the management of patients with HAIs frequently requires the administration of broader-spectrum antibiotic regimens due to the higher risk of acquiring multidrug-resistant organisms, which, in turn, promotes resistance. For this reason, even before using antibiotics correctly, it is necessary to prevent and control the spread of HAIs in our hospitals. In this narrative review, we present seven measures that healthcare workers, even if not directly involved in the tasks of infection prevention and control, must know, support, and embrace. We hope that this review may raise awareness among all healthcare professionals about the issues with the increasing rate of AMR and the ongoing efforts towards minimizing its rise.
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Affiliation(s)
| | - Corrado P Marini
- Jacobi Medical Center, New York Medical College, Bronx, NY 10461, USA
| | - John McNelis
- Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Federico Coccolini
- General, Emergency and Trauma Surgery Unit, Pisa University Hospital, 56125 Pisa, Italy
| | - Caterina Rizzo
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56125 Pisa, Italy
| | | | - Patrizio Petrone
- NYU Langone Hospital-Long Island, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA
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Zheng M, Chen H, Li X, Chen S, Shi Y, Hu H. Discovery of a novel antifungal agent: All-hydrocarbon stapling modification of peptide Aurein1.2. J Pept Sci 2024; 30:e3533. [PMID: 37431279 DOI: 10.1002/psc.3533] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 06/23/2023] [Accepted: 06/26/2023] [Indexed: 07/12/2023]
Abstract
Aurein1.2 is secreted by the Australian tree frog Litoria aurea and is active against a broad range of infectious microbes including bacteria, fungi, and viruses. Its antifungal potency has garnered considerable interest in developing novel classes of natural antifungal agents to fight pathogenic infection by fungi. However, serious pharmacological hurdles remain, hindering its clinical translation. To alleviate its susceptibility to proteolytic degradation and improve its antifungal activity, six conformationally locked peptides were synthesized through hydrocarbon stapling modification and evaluated for their physicochemical and antifungal parameters. Among them, SAU2-4 exhibited significant improvement in helicity levels, protease resistance, and antifungal activity compared to the template linear peptide Aurein1.2. These results confirmed the prominent role of hydrocarbon stapling modification in the manipulation of peptide pharmacological properties and enhanced the application potential of Aurein1.2 in the field of antifungal agent development.
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Affiliation(s)
- Mengjun Zheng
- Institute of Translational Medicine, Shanghai University, Shanghai, China
- School of Pharmacy, Naval Medical University, Shanghai, China
| | - Huixuan Chen
- School of Medicine, Shanghai University, Shanghai, China
| | - Xiang Li
- School of Pharmacy, Naval Medical University, Shanghai, China
| | - Si Chen
- School of Medicine, Shanghai University, Shanghai, China
| | - Yejiao Shi
- Institute of Translational Medicine, Shanghai University, Shanghai, China
| | - Honggang Hu
- School of Medicine, Shanghai University, Shanghai, China
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Ivagnes V, Menchinelli G, Liotti FM, De Carolis E, Torelli R, De Lorenzis D, Recine C, Sanguinetti M, D’Inzeo T, Posteraro B. Chip-Based Molecular Evaluation of a DNA Extraction Protocol for Candida Species from Positive Blood Cultures. Microorganisms 2023; 12:81. [PMID: 38257908 PMCID: PMC10821462 DOI: 10.3390/microorganisms12010081] [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: 10/30/2023] [Revised: 12/21/2023] [Accepted: 12/29/2023] [Indexed: 01/24/2024] Open
Abstract
The diagnosis of Candida bloodstream infection (BSI) may rely on a PCR-based analysis of a positive blood culture (PBC) obtained from the patient at the time of BSI. In this study, a yeast DNA extraction protocol for use on PBCs was developed and evaluated with the molecular mouse (MM) yeast blood (YBL) chip-based PCR assay, which allowed us to detect nine medically relevant Candida species. We studied 125 simulated or clinical PBCs for Candida species. A positive correlation between the DNA concentration and colony-forming unit count was found for simulated (Spearman's ρ = 0.58; p < 0.0001) and clinical (Spearman's ρ = 0.23, p = 0.09) PBCs. The extracted DNA yielded positive results with the MM YBL chip assay that agreed with the Candida species-level identification results for 63 (100%) of 63 isolates from simulated PBCs and 66 (99.5%) of 67 isolates from clinical PBCs. The false-negative result was for one C. tropicalis isolate that grew together with C. albicans in PBC. None of the 30 (Candida)-negative clinical BCs included as negative controls yielded a positive result with the MM YBL chip assay. Our DNA extraction protocol for the Candida species couples efficiency and simplicity together. Nevertheless, further studies are needed before it can be adopted for use with the MM YBL chip assay.
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Affiliation(s)
- Vittorio Ivagnes
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (V.I.); (D.D.L.); (C.R.); (T.D.); (B.P.)
| | - Giulia Menchinelli
- Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (G.M.); (F.M.L.); (E.D.C.); (R.T.)
| | - Flora Marzia Liotti
- Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (G.M.); (F.M.L.); (E.D.C.); (R.T.)
| | - Elena De Carolis
- Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (G.M.); (F.M.L.); (E.D.C.); (R.T.)
| | - Riccardo Torelli
- Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (G.M.); (F.M.L.); (E.D.C.); (R.T.)
| | - Desy De Lorenzis
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (V.I.); (D.D.L.); (C.R.); (T.D.); (B.P.)
| | - Cinzia Recine
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (V.I.); (D.D.L.); (C.R.); (T.D.); (B.P.)
| | - Maurizio Sanguinetti
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (V.I.); (D.D.L.); (C.R.); (T.D.); (B.P.)
- Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (G.M.); (F.M.L.); (E.D.C.); (R.T.)
| | - Tiziana D’Inzeo
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (V.I.); (D.D.L.); (C.R.); (T.D.); (B.P.)
- Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (G.M.); (F.M.L.); (E.D.C.); (R.T.)
| | - Brunella Posteraro
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (V.I.); (D.D.L.); (C.R.); (T.D.); (B.P.)
- Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endocrino Metaboliche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
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Wang Q, Cheng S, Wang Y, Li F, Chen J, Du W, Kang H, Wang Z. Global characteristics and trends in research on Candida auris. Front Microbiol 2023; 14:1287003. [PMID: 38125576 PMCID: PMC10731253 DOI: 10.3389/fmicb.2023.1287003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 11/13/2023] [Indexed: 12/23/2023] Open
Abstract
Introduction Candida auris, a fungal pathogen first reported in 2009, has shown strong resistance to azole antifungal drugs and has caused severe nosocomial outbreaks. It can also form biofilms, which can colonize patients' skin and transmit to others. Despite numerous reports of C. auris isolation in various countries, many studies have reported contradictory results. Method A bibliometric analysis was conducted using VOSviewer to summarize research trends and provide guidance for future research on controlling C. auris infection. The analysis revealed that the United States and the US CDC were the most influential countries and research institutions, respectively. For the researchers, Jacques F. Meis published the highest amount of related articles, and Anastasia P. Litvintseva's articles with the highest average citation rate. The most cited publications focused on clade classification, accurate identification technologies, nosocomial outbreaks, drug resistance, and biofilm formation. Keyword co-occurrence analysis revealed that the top five highest frequencies were for 'drug resistance,' 'antifungal susceptibility test,' 'infection,' 'Candida auris,' and 'identification.' The high-frequency keywords clustered into four groups: rapid and precise identification, drug resistance research, pathogenicity, and nosocomial transmission epidemiology studies. These clusters represent different study fields and current research hotspots of C. auris. Conclusion The bibliometric analysis identified the most influential country, research institution, and researcher, indicating current research trends and hotspots for controlling C. auris.
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Affiliation(s)
- Qihui Wang
- Laboratory of Microbiology, Department of Clinical Laboratory, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Shitong Cheng
- Laboratory of Microbiology, Department of Clinical Laboratory, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yinling Wang
- Laboratory of Microbiology, Department of Clinical Laboratory, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Fushun Li
- Laboratory of Microbiology, Department of Clinical Laboratory, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Jingjing Chen
- Laboratory of Microbiology, Department of Clinical Laboratory, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Wei Du
- National Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Hui Kang
- Laboratory of Microbiology, Department of Clinical Laboratory, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Zhongqing Wang
- Department of Information Centre, The First Hospital of China Medical University, Shenyang, Liaoning, China
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Sartelli M, Barie PS, Coccolini F, Abbas M, Abbo LM, Abdukhalilova GK, Abraham Y, Abubakar S, Abu-Zidan FM, Adebisi YA, Adamou H, Afandiyeva G, Agastra E, Alfouzan WA, Al-Hasan MN, Ali S, Ali SM, Allaw F, Allwell-Brown G, Amir A, Amponsah OKO, Al Omari A, Ansaloni L, Ansari S, Arauz AB, Augustin G, Awazi B, Azfar M, Bah MSB, Bala M, Banagala ASK, Baral S, Bassetti M, Bavestrello L, Beilman G, Bekele K, Benboubker M, Beović B, Bergamasco MD, Bertagnolio S, Biffl WL, Blot S, Boermeester MA, Bonomo RA, Brink A, Brusaferro S, Butemba J, Caínzos MA, Camacho-Ortiz A, Canton R, Cascio A, Cassini A, Cástro-Sanchez E, Catarci M, Catena R, Chamani-Tabriz L, Chandy SJ, Charani E, Cheadle WG, Chebet D, Chikowe I, Chiara F, Cheng VCC, Chioti A, Cocuz ME, Coimbra R, Cortese F, Cui Y, Czepiel J, Dasic M, de Francisco Serpa N, de Jonge SW, Delibegovic S, Dellinger EP, Demetrashvili Z, De Palma A, De Silva D, De Simone B, De Waele J, Dhingra S, Diaz JJ, Dima C, Dirani N, Dodoo CC, Dorj G, Duane TM, Eckmann C, Egyir B, Elmangory MM, Enani MA, Ergonul O, Escalera-Antezana JP, Escandon K, Ettu AWOO, Fadare JO, Fantoni M, Farahbakhsh M, Faro MP, Ferreres A, Flocco G, et alSartelli M, Barie PS, Coccolini F, Abbas M, Abbo LM, Abdukhalilova GK, Abraham Y, Abubakar S, Abu-Zidan FM, Adebisi YA, Adamou H, Afandiyeva G, Agastra E, Alfouzan WA, Al-Hasan MN, Ali S, Ali SM, Allaw F, Allwell-Brown G, Amir A, Amponsah OKO, Al Omari A, Ansaloni L, Ansari S, Arauz AB, Augustin G, Awazi B, Azfar M, Bah MSB, Bala M, Banagala ASK, Baral S, Bassetti M, Bavestrello L, Beilman G, Bekele K, Benboubker M, Beović B, Bergamasco MD, Bertagnolio S, Biffl WL, Blot S, Boermeester MA, Bonomo RA, Brink A, Brusaferro S, Butemba J, Caínzos MA, Camacho-Ortiz A, Canton R, Cascio A, Cassini A, Cástro-Sanchez E, Catarci M, Catena R, Chamani-Tabriz L, Chandy SJ, Charani E, Cheadle WG, Chebet D, Chikowe I, Chiara F, Cheng VCC, Chioti A, Cocuz ME, Coimbra R, Cortese F, Cui Y, Czepiel J, Dasic M, de Francisco Serpa N, de Jonge SW, Delibegovic S, Dellinger EP, Demetrashvili Z, De Palma A, De Silva D, De Simone B, De Waele J, Dhingra S, Diaz JJ, Dima C, Dirani N, Dodoo CC, Dorj G, Duane TM, Eckmann C, Egyir B, Elmangory MM, Enani MA, Ergonul O, Escalera-Antezana JP, Escandon K, Ettu AWOO, Fadare JO, Fantoni M, Farahbakhsh M, Faro MP, Ferreres A, Flocco G, Foianini E, Fry DE, Garcia AF, Gerardi C, Ghannam W, Giamarellou H, Glushkova N, Gkiokas G, Goff DA, Gomi H, Gottfredsson M, Griffiths EA, Guerra Gronerth RI, Guirao X, Gupta YK, Halle-Ekane G, Hansen S, Haque M, Hardcastle TC, Hayman DTS, Hecker A, Hell M, Ho VP, Hodonou AM, Isik A, Islam S, Itani KMF, Jaidane N, Jammer I, Jenkins DR, Kamara IF, Kanj SS, Jumbam D, Keikha M, Khanna AK, Khanna S, Kapoor G, Kapoor G, Kariuki S, Khamis F, Khokha V, Kiggundu R, Kiguba R, Kim HB, Kim PK, Kirkpatrick AW, Kluger Y, Ko WC, Kok KYY, Kotecha V, Kouma I, Kovacevic B, Krasniqi J, Krutova M, Kryvoruchko I, Kullar R, Labi KA, Labricciosa FM, Lakoh S, Lakatos B, Lansang MAD, Laxminarayan R, Lee YR, Leone M, Leppaniemi A, Hara GL, Litvin A, Lohsiriwat V, Machain GM, Mahomoodally F, Maier RV, Majumder MAA, Malama S, Manasa J, Manchanda V, Manzano-Nunez R, Martínez-Martínez L, Martin-Loeches I, Marwah S, Maseda E, Mathewos M, Maves RC, McNamara D, Memish Z, Mertz D, Mishra SK, Montravers P, Moro ML, Mossialos E, Motta F, Mudenda S, Mugabi P, Mugisha MJM, Mylonakis E, Napolitano LM, Nathwani D, Nkamba L, Nsutebu EF, O’Connor DB, Ogunsola S, Jensen PØ, Ordoñez JM, Ordoñez CA, Ottolino P, Ouedraogo AS, Paiva JA, Palmieri M, Pan A, Pant N, Panyko A, Paolillo C, Patel J, Pea F, Petrone P, Petrosillo N, Pintar T, Plaudis H, Podda M, Ponce-de-Leon A, Powell SL, Puello-Guerrero A, Pulcini C, Rasa K, Regimbeau JM, Rello J, Retamozo-Palacios MR, Reynolds-Campbell G, Ribeiro J, Rickard J, Rocha-Pereira N, Rosenthal VD, Rossolini GM, Rwegerera GM, Rwigamba M, Sabbatucci M, Saladžinskas Ž, Salama RE, Sali T, Salile SS, Sall I, Kafil HS, Sakakushev BE, Sawyer RG, Scatizzi M, Seni J, Septimus EJ, Sganga G, Shabanzadeh DM, Shelat VG, Shibabaw A, Somville F, Souf S, Stefani S, Tacconelli E, Tan BK, Tattevin P, Rodriguez-Taveras C, Telles JP, Téllez-Almenares O, Tessier J, Thang NT, Timmermann C, Timsit JF, Tochie JN, Tolonen M, Trueba G, Tsioutis C, Tumietto F, Tuon FF, Ulrych J, Uranues S, van Dongen M, van Goor H, Velmahos GC, Vereczkei A, Viaggi B, Viale P, Vila J, Voss A, Vraneš J, Watkins RR, Wanjiru-Korir N, Waworuntu O, Wechsler-Fördös A, Yadgarova K, Yahaya M, Yahya AI, Xiao Y, Zakaria AD, Zakrison TL, Zamora Mesia V, Siquini W, Darzi A, Pagani L, Catena F. Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action. World J Emerg Surg 2023; 18:50. [PMID: 37845673 PMCID: PMC10580644 DOI: 10.1186/s13017-023-00518-3] [Show More Authors] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 09/23/2023] [Indexed: 10/18/2023] Open
Abstract
Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
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Rashidi M, Bazi A, Ahmadzadeh A, Romeo O, Rezaei-Matehkolaei A, Abastabar M, Haghani I, Mirzaei S. The growth inhibitory and apoptotic effects of umbelliprenin in a mouse model of systemic candidiasis. J Appl Microbiol 2023; 134:lxad201. [PMID: 37669891 DOI: 10.1093/jambio/lxad201] [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: 06/12/2023] [Revised: 08/23/2023] [Accepted: 09/02/2023] [Indexed: 09/07/2023]
Abstract
AIMS Umbelliprenin has shown promising biological activities, including immunoregulatory, anti-inflammatory, and anti-cancer effects. The present study investigated the growth inhibitory and apoptotic effects of umbelliprenin against Candida albicans in a BALB/c mice model of disseminated candidiasis. METHODS AND RESULTS First, an antimicrobial assay via microdilution sensitivity test was performed. Then, twenty-five 6-week-old female BALB/c mice (20 ± 12 g) were divided into five groups of five mice, including one control group (no umbelliprenin treatment) and four experimental groups: C. albicans-infected mice treated with umbelliprenin at the doses of 5, 10, 20, and 40 mg kg -1. The brain, lung, kidney, spleen, and liver tissues were examined for fungal infection and histological lesions, and TUNEL staining was performed to assess apoptosis. The β-1, 3-glucan synthase assay was used to evaluate enzymatic activity, and gene expression analysis was also performed to investigate the transcriptional changes of ERG11, CDR1, ALS1, and HWP1 genes. The MIC of umbelliprenin was 1.5 mg mL-1. Our results showed that at the 40 mg kg -1 dose, umbelliprenin was able to eradicate fungal infection in BALB/c mice. The percentage of apoptotic cells in umbelliprenin-treated groups increased in a concentration-dependent manner. Umbelliprenin (40 mg kg -1) also inhibited the expression of β-1, 3-glucan synthase, and the genes involved in antifungal resistance (CDR1 and ERG11), as well as the expression of the genes encoding adhesins (ALS1 and HWP1). CONCLUSION Our results showed that umbelliprenin could promote antifungal effects, partly via inducing apoptosis.
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Affiliation(s)
- Mohsen Rashidi
- Department of Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari 48157-33971, Iran
- The Health of Plant and Livestock Products Research Center, Mazandaran University of Medical Sciences, Sari 48157-33971, Iran
| | - Ali Bazi
- Department of Laboratory Sciences, School of Allied Medical Sciences, Zabol University of Medical Sciences, Zabol 98616-15881, Iran
| | - Alireza Ahmadzadeh
- Department of Lab Sciences, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran 19839-69411, Iran
| | - Orazio Romeo
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 ME, Italy
- IRCCS-Centro Neurolesi Bonino-Pulejo, 98124 ME, Italy
| | - Ali Rezaei-Matehkolaei
- Department of Medical Mycology, School of Medicine, Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 61357-15794, Iran
| | - Mahdi Abastabar
- Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari 48157-33971, Iran
- Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari 48157-33971, Iran
| | - Iman Haghani
- Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari 48157-33971, Iran
- Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari 48157-33971, Iran
| | - Sepideh Mirzaei
- Department of Biology, Faculty of Sciences, Islamic Azad University Science and Research Branch, Tehran 14778-93855, Iran
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Di Vito M, Garzoli S, Rosato R, Mariotti M, Gervasoni J, Santucci L, Ovidi E, Cacaci M, Lombarini G, Torelli R, Urbani A, Sanguinetti M, Bugli F. A New Potential Resource in the Fight against Candida auris: the Cinnamomum zeylanicum Essential Oil in Synergy with Antifungal Drug. Microbiol Spectr 2023; 11:e0438522. [PMID: 36975835 PMCID: PMC10101117 DOI: 10.1128/spectrum.04385-22] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 03/10/2023] [Indexed: 03/29/2023] Open
Abstract
Candida auris is a multidrug-resistant fungus known to be a global public health problem. The skin-based transmission, together with the marked resistance to drugs, resulted in its rapid spread to all continents. The aim of this study was to identify an essential oil (EO) active in the fight against C. auris. A total of 15 EOs were tested against 10 clinical strains of C. auris. Cinnamomum zeylanicum EO (CZ-EO) was the most effective (MIC90 and MFC90 equal to 0.06% vol/vol). Three fractions obtained from CZ-EO, and the cinnamaldehyde (CIN), the major chemical compound, were tested to identify the principal compound effectives against C. auris. All CIN-containing samples showed anti-fungal activity. To study the synergy with fluconazole, CZ-EO, its active fraction (FR2), and CIN were tested in checkerboard tests. Results show that CZ-EO and FR2, but not CIN, synergize with fluconazole. Furthermore, only the copresence of CZ-EO or FR2 synergize with fluconazole at therapeutic concentrations of the drug (0.45 ± 0.32 μg/mL and 0.64 ± 0.67 μg/mL, respectively), while CIN only shows additive activity. In vivo studies conducted on Galleria mellonella larvae show the absence of toxicity of CZ-EO up to concentrations of 16% vol/vol, and the ability of CZ-EO to reactivate the efficacy of fluconazole when formulated at synergic concentrations. Finally, biochemical tests were made to study the mechanism of action of CZ-EO. These studies show that in the presence of both fluconazole and CZ-EO, the activity of fungal ATPases decreases and, at the same time, the amount of intracellular drug increases. IMPORTANCE This study highlights how small doses of CZ-EO are able to inhibit the secretion of fluconazole and promote its accumulation in the fungal cell. In this manner, the drug is able to exert its pharmacological effects bypassing the resistance of the yeast. If further studies will confirm this synergy, it will be possible to develop new therapeutic formulations active in the fight against C. auris resistances.
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Affiliation(s)
- M. Di Vito
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy
| | - S. Garzoli
- Dipartimento di Chimica e Tecnologie del Farmaco, Università di Roma Sapienza, Rome, Italy
| | - R. Rosato
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy
| | - M. Mariotti
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy
| | - J. Gervasoni
- UOC Chimica, Biochimica e Biologia Molecolare Clinica, Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - L. Santucci
- UOC Chimica, Biochimica e Biologia Molecolare Clinica, Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - E. Ovidi
- Department for Innovation in Biological, Agro-Food and Forest Systems DIBAF—University of Tuscia, Viterbo, Italy
| | - M. Cacaci
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - G. Lombarini
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy
| | - R. Torelli
- Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - A. Urbani
- UOC Chimica, Biochimica e Biologia Molecolare Clinica, Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - M. Sanguinetti
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - F. Bugli
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
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12
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Malik MA, AlHarbi L, Nabi A, Alzahrani KA, Narasimharao K, Kamli MR. Facile Synthesis of Magnetic Nigella Sativa Seeds: Advances on Nano-Formulation Approaches for Delivering Antioxidants and Their Antifungal Activity against Candida albicans. Pharmaceutics 2023; 15:pharmaceutics15020642. [PMID: 36839964 PMCID: PMC9965733 DOI: 10.3390/pharmaceutics15020642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 02/05/2023] [Accepted: 02/09/2023] [Indexed: 02/17/2023] Open
Abstract
This article reports on incorporating magnetic nanoparticles into natural carbon frameworks derived from Nigella Sativa seeds and their synthesis via co-precipitation reactions for application in biomedicine. The magnetic Nigella Sativa Seeds (Magnetic NSS), a metal oxide-based bio-nanomaterial, has shown excellent water diaper presence due to the presence of a wide range of oxygenous hydroxyl and carboxyl groups. The physicochemical properties of the composites were characterized extensively using Fourier transform infrared spectroscopy (FTIR), powder-X-ray diffraction (XRD), scanning electron microscopy (SEM), elemental analysis, transmission electron microscopy (TEM), and vibrating-sample magnetometer. Furthermore, synthesized magnetic NSS showed antioxidant and antifungal activity. The antifungal susceptibility was further tested against Candida albicans with a MIC value of 3.125 µg/mL. Analysis of antioxidant defense enzymes was determined quantitatively; the results suggested that antioxidant enzyme activity increase with increased magnetic NSS concentration. Furthermore, biofilm inhibition assay from scanning electron microscopy results revealed that magnetic NSS at the concentration of 3.5 μg/mL has anti-biofilm properties and can disrupt membrane integrity.
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Affiliation(s)
- Maqsood Ahmad Malik
- Chemistry Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia
- Correspondence: (M.A.M.); (M.R.K.)
| | - Laila AlHarbi
- Chemistry Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia
| | - Arshid Nabi
- Department of Chemistry, University of Malaya, Kuala Lumpur 50603, Malaysia
| | - Khalid Ahmed Alzahrani
- Chemistry Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia
| | - Katabathini Narasimharao
- Chemistry Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia
| | - Majid Rasool Kamli
- Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia
- Center of Excellence in Bionanoscience Research, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia
- Correspondence: (M.A.M.); (M.R.K.)
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13
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Zhang Z, Yu W, Li G, He Y, Shi Z, Wu J, Ma X, Zhu Y, Zhao L, Liu S, Wei Y, Xue J, Guo S, Gao Z. Characteristics of oral microbiome of healthcare workers in different clinical scenarios: a cross-sectional analysis. BMC Oral Health 2022; 22:481. [PMID: 36357898 PMCID: PMC9648452 DOI: 10.1186/s12903-022-02501-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 10/12/2022] [Indexed: 11/11/2022] Open
Abstract
The environment of healthcare institutes (HCIs) potentially affects the internal microecology of medical workers, which is reflected not only in the well-studied gut microbiome but also in the more susceptible oral microbiome. We conducted a prospective cross-sectional cohort study in four hospital departments in Central China. Oropharyngeal swabs from 65 healthcare workers were collected and analyzed using 16S rRNA gene amplicon sequencing. The oral microbiome of healthcare workers exhibited prominent deviations in diversity, microbial structure, and predicted function. The coronary care unit (CCU) samples exhibited robust features and stability, with significantly higher abundances of genera such as Haemophilus, Fusobacterium, and Streptococcus, and a lower abundance of Prevotella. Functional prediction analysis showed that vitamin, nucleotide, and amino acid metabolisms were significantly different among the four departments. The CCU group was at a potential risk of developing periodontal disease owing to the increased abundance of F. nucleatum. Additionally, oral microbial diversification of healthcare workers was related to seniority. We described the oral microbiome profile of healthcare workers in different clinical scenarios and demonstrated that community diversity, structure, and potential functions differed markedly among departments. Intense modulation of the oral microbiome of healthcare workers occurs because of their original departments, especially in the CCU.
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Affiliation(s)
- Zhixia Zhang
- Nursing Department, Linfen Central Hospital, 041000 Shanxi, Shanxi China
| | - Wenyi Yu
- grid.411634.50000 0004 0632 4559Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, China
| | - Guangyao Li
- Science and Education Department, Linfen Central Hospital, Hainan, Shanxi China
| | - Yukun He
- grid.411634.50000 0004 0632 4559Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, China
| | - Zhiming Shi
- Cardiology Department, Linfen Central Hospital, Hainan, Shanxi China
| | - Jing Wu
- Nursing Department, Linfen Central Hospital, 041000 Shanxi, Shanxi China
| | - Xinqian Ma
- grid.411634.50000 0004 0632 4559Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, China
| | - Yu Zhu
- Science and Education Department, Linfen Central Hospital, Hainan, Shanxi China
| | - Lili Zhao
- grid.411634.50000 0004 0632 4559Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, China
| | - Siqin Liu
- grid.440653.00000 0000 9588 091XThe Stomatology College of Binzhou Medical University, Yantai, Shandong China
| | - Yue Wei
- grid.263452.40000 0004 1798 4018Nursing College of Shanxi Medical University, Shanxi, China
| | - Jianbo Xue
- grid.411634.50000 0004 0632 4559Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, China
| | - Shuming Guo
- Nursing Department, Linfen Central Hospital, 041000 Shanxi, Shanxi China
| | - Zhancheng Gao
- grid.411634.50000 0004 0632 4559Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, China ,grid.411634.50000 0004 0632 4559Department of Pulmonary and Critical Care Medicine, Peking University People’s Hospital, 100044 Beijing, China
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Fungicidal activity of human antimicrobial peptides and their synergistic interaction with common antifungals against multidrug-resistant Candida auris. Int Microbiol 2022; 26:165-177. [PMID: 36329309 DOI: 10.1007/s10123-022-00290-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 10/12/2022] [Accepted: 10/25/2022] [Indexed: 11/05/2022]
Abstract
Emergence of Candida auris, a multidrug-resistant yeast, demonstrates the urgent need for novel antifungal agents. Human antimicrobial peptides (AMPs) are naturally occurring molecules with wide spectrum antimicrobial activity, particularly against a variety of fungi. Therefore, this study examined the antifungal activity of seven different human AMPs against C. auris following the CLSI guidelines. The antifungal activity was further assessed using time kill curve and cell viability assays. For combination interaction, effectiveness of these peptides with three antifungals, fluconazole, amphotericin B, and caspofungin was done following standard protocols. To elucidate the antifungal mechanism, the effects of peptides on membrane permeability were investigated using propidium iodide staining method and confocal imaging. Antifungal susceptibility results showed that all the examined peptides possessed fungicidal effect against C. auris at different levels, with human β-defensin-3 being the most potent antifungal with MIC values ranging from 3.125 to 12.5 µg/ml. Time kill curves further confirmed the killing effect of all the tested peptides. Viability assay showed a significant decrease in the percentage of viable cells exposed to different inhibitory and fungicidal concentrations of each peptide (p < 0.01). Furthermore, peptides showed mostly synergistic interaction when combined with conventional antifungal drugs, with caspofungin showing 100% synergy when combined with different AMPs. As antifungal mechanism, peptides disrupted the membrane permeability at concentrations that correlated with the inhibition of growth. Overall, the findings of this study point towards the application of the tested peptides as a monotherapy or as a combination therapy with antifungal drugs to treat multidrug-resistant C. auris infections.
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15
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Agyeman WY, Bisht A, Gopinath A, Cheema AH, Chaludiya K, Khalid M, Nwosu M, Konka S, Khan S. A Systematic Review of Antibiotic Resistance Trends and Treatment Options for Hospital-Acquired Multidrug-Resistant Infections. Cureus 2022; 14:e29956. [PMID: 36381838 PMCID: PMC9635809 DOI: 10.7759/cureus.29956] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 10/05/2022] [Indexed: 11/07/2022] Open
Abstract
Antimicrobial resistance is a major public health challenge described by the World Health Organization as one of the top 10 public health challenges worldwide. Drug-resistant microbes contribute significantly to morbidity and mortality in the hospital, especially in the critical care unit. The primary etiology of increasing antibiotic resistance is inappropriate and excessive use of antibiotics. The alarming rise of drug-resistant microbes worldwide threatens to erode our ability to treat infections with our current armamentarium of antibiotics. Unfortunately, the pace of development of new antibiotics by the pharmaceutical industry has not kept up with rising resistance to expand our options to treat microbial infections. The costs of antibiotic resistance include death and disability, extended hospital stays due to prolonged sickness, need for expensive therapies, rising healthcare expenditure, reduced productivity from time out of the workforce, and rising penury. This review sums up the common mechanisms, trends, and treatment options for hospital-acquired multidrug-resistant microbes.
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Affiliation(s)
- Walter Y Agyeman
- Internal Medicine, Piedmont Athens Regional Medical Center, Georgia, USA
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Aakash Bisht
- Internal Medicine, Government Medical College, Amritsar, Amritsar, IND
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Ankit Gopinath
- Internal Medicine, Kasturba Medical College, Manipal, Manipal, IND
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Ameer Haider Cheema
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Keyur Chaludiya
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Maham Khalid
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Marcellina Nwosu
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Srujana Konka
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Safeera Khan
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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16
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Pezzotti G, Kobara M, Nakaya T, Imamura H, Asai T, Miyamoto N, Adachi T, Yamamoto T, Kanamura N, Ohgitani E, Marin E, Zhu W, Nishimura I, Mazda O, Nakata T, Makimura K. Raman Study of Pathogenic Candida auris: Imaging Metabolic Machineries in Reaction to Antifungal Drugs. Front Microbiol 2022; 13:896359. [PMID: 35694304 PMCID: PMC9175029 DOI: 10.3389/fmicb.2022.896359] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 04/25/2022] [Indexed: 12/02/2022] Open
Abstract
The multidrug-resistant Candida auris often defies treatments and presently represents a worldwide public health threat. Currently, the ergosterol-targeting Amphotericin B (AmB) and the DNA/RNA-synthesis inhibitor 5-flucytosine (5-FC) are the two main drugs available for first-line defense against life-threatening Candida auris infections. However, important aspects of their mechanisms of action require further clarification, especially regarding metabolic reactions of yeast cells. Here, we applied Raman spectroscopy empowered with specifically tailored machine-learning algorithms to monitor and to image in situ the susceptibility of two Candida auris clades to different antifungal drugs (LSEM 0643 or JCM15448T, belonging to the East Asian Clade II; and, LSEM 3673 belonging to the South African Clade III). Raman characterizations provided new details on the mechanisms of action against Candida auris Clades II and III, while also unfolding differences in their metabolic reactions to different drugs. AmB treatment induced biofilm formation in both clades, but the formed biofilms showed different structures: a dense and continuous biofilm structure in Clade II, and an extra-cellular matrix with a “fluffy” and discontinuous structure in Clade III. Treatment with 5-FC caused no biofilm formation but yeast-to-hyphal or pseudo-hyphal morphogenesis in both clades. Clade III showed a superior capacity in reducing membrane permeability to the drug through chemically tailoring chitin structure with a high degree of acetylation and fatty acids networks with significantly elongated chains. This study shows the suitability of the in situ Raman method in characterizing susceptibility and stress response of different C. auris clades to antifungal drugs, thus opening a path to identifying novel clinical solutions counteracting the spread of these alarming pathogens.
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Affiliation(s)
- Giuseppe Pezzotti
- Ceramic Physics Laboratory, Kyoto Institute of Technology, Kyoto, Japan
- Department of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Department of Orthopedic Surgery, Tokyo Medical University, Tokyo, Japan
- Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
- The Center for Advanced Medical Engineering and Informatics, Osaka University, Osaka, Japan
- *Correspondence: Giuseppe Pezzotti
| | - Miyuki Kobara
- Division of Pathological Science, Department of Clinical Pharmacology, Kyoto Pharmaceutical University, Kyoto, Japan
| | - Tamaki Nakaya
- Ceramic Physics Laboratory, Kyoto Institute of Technology, Kyoto, Japan
| | - Hayata Imamura
- Ceramic Physics Laboratory, Kyoto Institute of Technology, Kyoto, Japan
| | - Tenma Asai
- Ceramic Physics Laboratory, Kyoto Institute of Technology, Kyoto, Japan
| | - Nao Miyamoto
- Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tetsuya Adachi
- Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Toshiro Yamamoto
- Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Narisato Kanamura
- Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Eriko Ohgitani
- Department of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Elia Marin
- Ceramic Physics Laboratory, Kyoto Institute of Technology, Kyoto, Japan
- Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Wenliang Zhu
- Ceramic Physics Laboratory, Kyoto Institute of Technology, Kyoto, Japan
| | - Ichiro Nishimura
- Division of Advanced Prosthodontics, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, Los Angeles, CA, United States
| | - Osam Mazda
- Department of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tetsuo Nakata
- Division of Pathological Science, Department of Clinical Pharmacology, Kyoto Pharmaceutical University, Kyoto, Japan
| | - Koichi Makimura
- Medical Mycology, Graduate School of Medicine, Teikyo University, Tokyo, Japan
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17
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Kamli MR, Malik MA, Lone SA, Sabir JSM, Mattar EH, Ahmad A. Beta vulgaris Assisted Fabrication of Novel Ag-Cu Bimetallic Nanoparticles for Growth Inhibition and Virulence in Candida albicans. Pharmaceutics 2021; 13:1957. [PMID: 34834372 PMCID: PMC8621205 DOI: 10.3390/pharmaceutics13111957] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 11/12/2021] [Accepted: 11/15/2021] [Indexed: 01/03/2023] Open
Abstract
Beta vulgaris extract contains water-soluble red pigment betanin and is used as a food colorant. In this study, the biogenic Ag-Cu bimetallic nanoparticles were synthesized and characterized by different spectroscopic and microscopic techniques, including UV-Visible, FTIR, TEM. SEM-EDX, XRD, and TGA. Further, Ag-Cu bimetallic nanoparticles capped with Beta vulgaris biomolecules were evaluated for their antifungal activity against Candida albicans via targeting its major virulence factors, including adherence, yeast to hyphae transition, extracellular enzyme secretion, biofilm formation, and the expression of genes related to these pathogenic traits by using standard methods. C. albicans is an opportunistic human fungal pathogen that causes significant morbidity and mortality, mainly in immunocompromised patients. The current antifungal therapy is limited with various shortcomings such as host toxicity and developing multidrug resistance. Therefore, the development of novel antifungal agents is urgently required. Furthermore, NPs were screened for cell viability and cytotoxicity effect. Antifungal susceptibility testing showed potent antifungal activity of the Ag-Cu bimetallic NPs with a significant inhibitory effect on adherence, yeast to hyphae transition, extracellular enzymes secretion, and formation of biofilms in C. albicans at sub-inhibitory and inhibitory concentrations. The RT-qPCR results at an MIC value of the NPs exhibited a varying degree of downregulation in expression levels of virulence genes. Results also revealed the dose-dependent effect of NPs on cellular viability (up to 100%) using MUSE cell analyzer. Moreover, the low cytotoxicity effect of bimetallic NPs has been observed using haemolytic assay. The overall results indicated that the newly synthesized Ag-Cu bimetallic NPs capped with Beta vulgaris are proven to possess a potent anticandidal activity, by affecting the vital pathogenic factors of C. albicans.
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Affiliation(s)
- Majid Rasool Kamli
- Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia; (J.S.M.S.); (E.H.M.)
- Center of Excellence in Bionanoscience Research, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia
| | - Maqsood Ahmad Malik
- Chemistry Department, Faculty of Sciences, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia
| | - Shabir Ahmad Lone
- Clinical Microbiology and Infectious Diseases, Faculty of Health Sciences, School of Pathology, University of the Witwatersrand, Johannesburg 2193, South Africa; (S.A.L.); (A.A.)
| | - Jamal S. M. Sabir
- Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia; (J.S.M.S.); (E.H.M.)
- Center of Excellence in Bionanoscience Research, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia
| | - Ehab H. Mattar
- Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia; (J.S.M.S.); (E.H.M.)
| | - Aijaz Ahmad
- Clinical Microbiology and Infectious Diseases, Faculty of Health Sciences, School of Pathology, University of the Witwatersrand, Johannesburg 2193, South Africa; (S.A.L.); (A.A.)
- Infection Control Unit, Charlotte Maxeke Johannesburg Academic Hospital, National Health Laboratory Service, Johannesburg 2193, South Africa
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Flores-Maldonado O, González GM, Andrade A, Montoya A, Treviño-Rangel R, Silva-Sánchez A, Becerril-García MA. Dissemination of Candida auris to deep organs in neonatal murine invasive candidiasis. Microb Pathog 2021; 161:105285. [PMID: 34774701 DOI: 10.1016/j.micpath.2021.105285] [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: 09/24/2021] [Revised: 11/03/2021] [Accepted: 11/04/2021] [Indexed: 10/19/2022]
Abstract
Candida auris is an emerging multidrug resistant fungal pathogen, which represents a major challenge for newborns systemic infections worldwide. Management of C. auris infections is complicated due to its intrinsic antifungal resistance and the limited information available on its pathogenesis, particularly during neonatal period. In this study, we developed a murine model of C. auris neonatal invasive infection. C. auris dissemination was evaluated by fungal burden and histopathological analysis of lung, brain, liver, kidney, and spleen at different time intervals. We found fungal cells in all the analyzed tissues, neonatal liver and brain were the most susceptible tissues to fungal invasion. This model will help to better understand pathogenesis mechanisms and facilitate strategies for control and prevention of C. auris infections in newborns.
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Affiliation(s)
- Orlando Flores-Maldonado
- Departamento de Microbiología, Universidad Autónoma de Nuevo León, Facultad de Medicina y Hospital Universitario "Dr. José Eleuterio González", Av. Francisco I. Madero, Mitras Centro, 64460, Monterrey, Mexico
| | - Gloria M González
- Departamento de Microbiología, Universidad Autónoma de Nuevo León, Facultad de Medicina y Hospital Universitario "Dr. José Eleuterio González", Av. Francisco I. Madero, Mitras Centro, 64460, Monterrey, Mexico
| | - Angel Andrade
- Departamento de Microbiología, Universidad Autónoma de Nuevo León, Facultad de Medicina y Hospital Universitario "Dr. José Eleuterio González", Av. Francisco I. Madero, Mitras Centro, 64460, Monterrey, Mexico
| | - Alexandra Montoya
- Departamento de Microbiología, Universidad Autónoma de Nuevo León, Facultad de Medicina y Hospital Universitario "Dr. José Eleuterio González", Av. Francisco I. Madero, Mitras Centro, 64460, Monterrey, Mexico
| | - Rogelio Treviño-Rangel
- Departamento de Microbiología, Universidad Autónoma de Nuevo León, Facultad de Medicina y Hospital Universitario "Dr. José Eleuterio González", Av. Francisco I. Madero, Mitras Centro, 64460, Monterrey, Mexico
| | - Aarón Silva-Sánchez
- Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Miguel A Becerril-García
- Departamento de Microbiología, Universidad Autónoma de Nuevo León, Facultad de Medicina y Hospital Universitario "Dr. José Eleuterio González", Av. Francisco I. Madero, Mitras Centro, 64460, Monterrey, Mexico.
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Hedera rhombea inhibits the biofilm formation of Candida, thereby increases the susceptibility to antifungal agent, and reduces infection. PLoS One 2021; 16:e0258108. [PMID: 34614005 PMCID: PMC8494327 DOI: 10.1371/journal.pone.0258108] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 09/17/2021] [Indexed: 12/27/2022] Open
Abstract
Candida is an opportunistic pathogen and a common cause of fungal infections worldwide. Anti-fungal use against Candida infections has resulted in the appearance of resistant strains. The limited choice of anti-fungal therapy means alternative strategies are needed to control fungal infectious diseases. The aim of this study was to evaluate the inhibition of Candida biofilm formation by Hedera rhombea (Korean name: songak) extract. Biofilm formation was assessed using the crystal violet assay which showed a dose dependent reduction in the presence of extract with the biofilm formation inhibitory concentration of C. albicans (IC50 = 12.5μg/ml), C. tropicalis var. tropicalis (IC50 = 25μg/ml), C. parapsilosis var. parapsilosis (IC50 = 6.25μg/ml), C. glabrata (IC50 = 6.25μg/ml), C. tropicalis (IC50 = 12.5μg/ml), and C. parapsilosis (IC50 = 12.5μg/ml) without directly reducing Candida growth. Treatment with 6.25μg/mL of extract increased the antifungal susceptibility to miconazole from 32% decreasing of fungal growth to 98.8% of that based on the fungal growth assay. Treatment of extract dose-dependently reduced the dimorphic transition of Candida based on the dimorphic transition assay and treatment of 3.125μg/mL of extract completely blocked the adherence of Candida to the HaCaT cells. To know the molecular mechanisms of biofilm formation inhibition by extract, qRT-PCR analysis was done, and the extract was found to dose dependently reduce the expression of hyphal-associated genes (ALS3, ECE1, HWP1, PGA50, and PBR1), extracellular matrix genes (GSC1, ZAP1, ADH5, and CSH1), Ras1-cAMP-PKA pathway genes (CYR1, EFG1, and RAS1), Cph2-Tec1 pathway gene (TEC1) and MAP kinases pathway gene (HST7). In this study, Hedera rhombea extract showed inhibition of fungal biofilm formation, activation of antifungal susceptibility, and reduction of infection. These results suggest that fungal biofilm formation is good screen for developing the antifungal adjuvant and Hedera rhombea extract should be a good candidate against biofilm-related fungal infection.
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Herrero-de-Dios C, Román E, Pla J, Alonso-Monge R. Hog1 Controls Lipids Homeostasis Upon Osmotic Stress in Candida albicans. J Fungi (Basel) 2020; 6:jof6040355. [PMID: 33321998 PMCID: PMC7770603 DOI: 10.3390/jof6040355] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 11/28/2020] [Accepted: 12/08/2020] [Indexed: 12/02/2022] Open
Abstract
As opportunistic pathogen, Candida albicans adapts to different environmental conditions and its corresponding stress. The Hog1 MAPK (Mitogen Activated Protein Kinase) was identified as the main MAPK involved in the response to osmotic stress. It was later shown that this MAPK is also involved in the response to a variety of stresses and therefore, its role in virulence, survival to phagocytes and establishment as commensal in the mouse gastrointestinal tract was reported. In this work, the role of Hog1 in osmotic stress is further analyzed, showing that this MAPK is involved in lipid homeostasis. The hog1 mutant accumulates lipid droplets when exposed to osmotic stress, leading to an increase in cell permeability and delaying the endocytic trafficking routes. Cek1, a MAPK also implicated in the response to osmotic challenge, did not play a role in lipid homeostasis indicating that Hog1 is the main MAP kinase in this response. The alteration on lipid metabolism observed in hog1 mutants is proposed to contribute to the sensitivity to osmotic stress.
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Affiliation(s)
- Carmen Herrero-de-Dios
- Servicio de Bioquímica, Hospital Universitario Ramón y Cajal, Ctra. Colmenar Km 9, 28034 Madrid, Spain;
| | - Elvira Román
- Departamento de Microbiología y Parasitología-IRYCIS, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, 28040 Madrid, Spain; (E.R.); (J.P.)
| | - Jesús Pla
- Departamento de Microbiología y Parasitología-IRYCIS, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, 28040 Madrid, Spain; (E.R.); (J.P.)
| | - Rebeca Alonso-Monge
- Departamento de Microbiología y Parasitología-IRYCIS, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, 28040 Madrid, Spain; (E.R.); (J.P.)
- Correspondence: ; Tel.: +34-91-394-1888
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