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Santos ALSD, Branquinha MH. New Strategies to Combat Human Fungal Infections. J Fungi (Basel) 2024; 10:880. [PMID: 39728376 DOI: 10.3390/jof10120880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 12/12/2024] [Accepted: 12/16/2024] [Indexed: 12/28/2024] Open
Abstract
Over the past few decades, numerous reports have highlighted the significant rise in fungal infections worldwide, contributing to considerable morbidity, mortality, and escalating healthcare costs [...].
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Affiliation(s)
- André Luis Souza Dos Santos
- Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes (IMPG), Centro de Ciências da Saúde (CCS), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, RJ, Brazil
- Rede Micologia RJ-Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Rio de Janeiro 21941-902, RJ, Brazil,
| | - Marta Helena Branquinha
- Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes (IMPG), Centro de Ciências da Saúde (CCS), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, RJ, Brazil
- Rede Micologia RJ-Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Rio de Janeiro 21941-902, RJ, Brazil,
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2
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Kondori N, Jaén-Luchoro D, Karlsson R, Abedzaedeh B, Hammarström H, Jönsson B. Exophiala species in household environments and their antifungal resistance profile. Sci Rep 2024; 14:17622. [PMID: 39085337 PMCID: PMC11291800 DOI: 10.1038/s41598-024-68166-4] [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: 03/01/2024] [Accepted: 07/22/2024] [Indexed: 08/02/2024] Open
Abstract
The black fungus Exophiala causes a wide range of infections from superficial to subcutaneous, but also invasive fungal infections in immunocompromised patients as well as healthy individuals. In addition, Exophiala, is a common colonizer of the air ways of patients with cystic fibrosis. However, the source of infection and mode of transmission is still unclear. The aim of this study was to investigate the presence of Exophiala in samples collected from Swedish indoor environments. We found that the Exophiala species were commonly found in dishwashers and that Exophiala dermatitidis was the most common Exophiala species, being identified in 70% (26 out of the 37) of samples. Almost all E. dermatitidis isolates had the ability to grow at 42 °C (P = 0.0002) and were catalase positive. Voriconazole and posaconazole exhibited the lowest MICs, while caspofungin and anidulafungin lack the antifungal activities in vitro. Future studies are needed to illuminate the transmission mode of the fungi.
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Affiliation(s)
- Nahid Kondori
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Box 7193, 402 34, Gothenburg, Sweden.
- Department of Clinical Microbiology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.
| | - Daniel Jaén-Luchoro
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Box 7193, 402 34, Gothenburg, Sweden
- Department of Clinical Microbiology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden
| | - Roger Karlsson
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Box 7193, 402 34, Gothenburg, Sweden
- Department of Clinical Microbiology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden
- Nanoxis Consulting AB, Gothenburg, Sweden
| | - Bahman Abedzaedeh
- Department of Clinical Microbiology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden
| | - Helena Hammarström
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Box 7193, 402 34, Gothenburg, Sweden
- Department of Infectious Diseases, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden
| | - Bodil Jönsson
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Box 7193, 402 34, Gothenburg, Sweden
- Department of Clinical Microbiology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden
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3
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Smith K, Stone W, Botha A, Steffen H, Wolfaardt G. Riverine mycobiome dynamics: From South African tributaries to laboratory bioreactors. Mycology 2024; 15:631-650. [PMID: 39678638 PMCID: PMC11636148 DOI: 10.1080/21501203.2023.2278309] [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: 06/18/2023] [Accepted: 10/28/2023] [Indexed: 12/17/2024] Open
Abstract
Riverine fungi have the capacity for both pathogenicity, pertinent for countries with elevated immunosuppressed individuals, and bioremediation potential. The purpose was (i) to screen for the presence of clinically relevant riverine fungi and associations with anthropogenic influence, and (ii) the acclimatisation of environmental communities toward potential bioremediation application. Communities were harvested from polluted rivers in Stellenbosch, South Africa, and mycobiomes characterised by high-throughput amplicon sequencing. The remainder of the biomass was inoculated into continuous bioreactors with filtered river water or sterile minimal medium. Seven weeks later, the mycobiomes were re-sequenced. At least nine clinically relevant species were detected, including agents of mycoses belonging to the genus Candida. The occurrence of genera that harbour opportunisticstrains was significantly higher (P = 0.04) at more polluted sites. Moreover, positive correlations occured between some genera and pollution indices, demonstrating the potential of fungi for addition to water quality indicators. Despite biomass increase, almost all pathogens were undetectable after seven weeks, demonstrating less resilience in conditions mimicking rivers. Thus, when screening riverine biomes for bioremediation potential, ambient reactors select against human pathogens. This indicates a transient introduction of allochthonous opportunistic species into rivers due to insufficient sanitation, and the potential of bioremediation strategies that selects for environmental rather than pathogenic traits.
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Affiliation(s)
- Katrin Smith
- Department of Microbiology, University of Stellenbosch, Stellenbosch, South Africa
| | - Wendy Stone
- Department of Microbiology, University of Stellenbosch, Stellenbosch, South Africa
| | - Alfred Botha
- Department of Microbiology, University of Stellenbosch, Stellenbosch, South Africa
| | - Heidi Steffen
- Department of Microbiology, University of Stellenbosch, Stellenbosch, South Africa
| | - Gideon Wolfaardt
- Department of Microbiology, University of Stellenbosch, Stellenbosch, South Africa
- Department of Chemistry and Biology, Toronto Metropolitan University, Toronto, Canada
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Hilmy KMH, Kishk FNM, Shahen EBA, Sobh EA, Hawata MA. New pyrrole derivatives as DNA gyrase and 14α-demethylase inhibitors: Design, synthesis, antimicrobial evaluation, and molecular docking. Drug Dev Res 2023; 84:1204-1230. [PMID: 37165799 DOI: 10.1002/ddr.22080] [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: 12/29/2022] [Revised: 03/01/2023] [Accepted: 03/12/2023] [Indexed: 05/12/2023]
Abstract
An efficient one-pot reaction utilizing readily available chemical reagents was used to prepare novel 2-amino-1,5-diaryl-1H-pyrrole-3-carbonitrile derivatives and the structures of these compounds were validated by spectroscopic data and elemental analyses. All the synthetic compounds were evaluated for their antimicrobial activities (MZI assay). The tested compounds proved high activities on Staphylococcus aureus (Gram-positive bacteria) and Candida albicans (Pathogenic fungi). However, they did not show any activity on Escherichia coli (Gram-negative bacteria). The most effective compounds in MZI assay 7c, 9a, 9b, 11a, and 11b were selected to determine their MIC on S. aureus and C. albicans. Furthermore, DNA gyrase and 14-α demethylase inhibitory assays were performed to study the inhibitory activities of 7c, 9a, 9b, 11a, and 11b. The results illustrated that compound 9b was the most DNA gyrase inhibitor (IC50 of 0.0236 ± 0.45 µM, which was 1.3- fold higher than gentamicin reference IC50 values of 0.0323 ± 0.81 µM). In addition, compound 9b demonstrated the highest 14-α demethylase inhibitory effect with IC50 of 0.0013 ± 0.02 µM, compared to ketoconazole (IC50 of 0.0008 ± 0.03 µM) and fluconazole (IC50 of 0.00073 ± 0.01 µM), as antifungal reference drugs. Lastly, docking studies were performed to rationalize the dual inhibitory activities of the highly active compounds on both DNA gyrase and 14-α demethylase enzymes.
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Affiliation(s)
- Khaled M H Hilmy
- Department of Chemistry, Faculty of Science, El-Menoufia University, Shebin El-Kom, Egypt
| | - Fawzya N M Kishk
- Department of Chemistry, Faculty of Science, El-Menoufia University, Shebin El-Kom, Egypt
| | - Esmat B A Shahen
- Depatment of Biochemistry, Faculty of Medicine, Al-Azhar University for Girls, Cairo, Egypt
| | - Eman A Sobh
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Menoufia University, Menoufia, Shebin El-Kom, Egypt
| | - Mohamed A Hawata
- Department of Chemistry, Faculty of Science, El-Menoufia University, Shebin El-Kom, Egypt
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5
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Fayed EA, Ebrahim MA, Fathy U, Saeed HSE, Khalaf WS. Evaluation of quinoxaline derivatives as potential ergosterol biosynthesis inhibitors: design, synthesis, ADMET, molecular docking studies, and antifungal activities. J Mol Struct 2022. [DOI: 10.1016/j.molstruc.2022.133578] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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6
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Marine Cyclic Peptides: Antimicrobial Activity and Synthetic Strategies. Mar Drugs 2022; 20:md20060397. [PMID: 35736200 PMCID: PMC9230156 DOI: 10.3390/md20060397] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 06/06/2022] [Accepted: 06/13/2022] [Indexed: 01/29/2023] Open
Abstract
Oceans are a rich source of structurally unique bioactive compounds from the perspective of potential therapeutic agents. Marine peptides are a particularly interesting group of secondary metabolites because of their chemistry and wide range of biological activities. Among them, cyclic peptides exhibit a broad spectrum of antimicrobial activities, including against bacteria, protozoa, fungi, and viruses. Moreover, there are several examples of marine cyclic peptides revealing interesting antimicrobial activities against numerous drug-resistant bacteria and fungi, making these compounds a very promising resource in the search for novel antimicrobial agents to revert multidrug-resistance. This review summarizes 174 marine cyclic peptides with antibacterial, antifungal, antiparasitic, or antiviral properties. These natural products were categorized according to their sources—sponges, mollusks, crustaceans, crabs, marine bacteria, and fungi—and chemical structure—cyclic peptides and depsipeptides. The antimicrobial activities, including against drug-resistant microorganisms, unusual structural characteristics, and hits more advanced in (pre)clinical studies, are highlighted. Nocathiacins I–III (91–93), unnarmicins A (114) and C (115), sclerotides A (160) and B (161), and plitidepsin (174) can be highlighted considering not only their high antimicrobial potency in vitro, but also for their promising in vivo results. Marine cyclic peptides are also interesting models for molecular modifications and/or total synthesis to obtain more potent compounds, with improved properties and in higher quantity. Solid-phase Fmoc- and Boc-protection chemistry is the major synthetic strategy to obtain marine cyclic peptides with antimicrobial properties, and key examples are presented guiding microbiologist and medicinal chemists to the discovery of new antimicrobial drug candidates from marine sources.
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7
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Willaert RG, Kayacan Y, Devreese B. The Flo Adhesin Family. Pathogens 2021; 10:pathogens10111397. [PMID: 34832553 PMCID: PMC8621652 DOI: 10.3390/pathogens10111397] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 10/11/2021] [Accepted: 10/25/2021] [Indexed: 12/14/2022] Open
Abstract
The first step in the infection of fungal pathogens in humans is the adhesion of the pathogen to host tissue cells or abiotic surfaces such as catheters and implants. One of the main players involved in this are the expressed cell wall adhesins. Here, we review the Flo adhesin family and their involvement in the adhesion of these yeasts during human infections. Firstly, we redefined the Flo adhesin family based on the domain architectures that are present in the Flo adhesins and their functions, and set up a new classification of Flo adhesins. Next, the structure, function, and adhesion mechanisms of the Flo adhesins whose structure has been solved are discussed in detail. Finally, we identified from Pfam database datamining yeasts that could express Flo adhesins and are encountered in human infections and their adhesin architectures. These yeasts are discussed in relation to their adhesion characteristics and involvement in infections.
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Affiliation(s)
- Ronnie G. Willaert
- Research Group Structural Biology Brussels (SBB), Vrije Universiteit Brussel (VUB), 1050 Brussels, Belgium;
- Alliance Research Group VUB-UGent NanoMicrobiology (NAMI), 1050 Brussels, Belgium;
- International Joint Research Group VUB-EPFL NanoBiotechnology & NanoMedicine (NANO), Vrije Universiteit Brussel (VUB), 1050 Brussels, Belgium
- Correspondence: ; Tel.: +32-2629-1846
| | - Yeseren Kayacan
- Research Group Structural Biology Brussels (SBB), Vrije Universiteit Brussel (VUB), 1050 Brussels, Belgium;
- Alliance Research Group VUB-UGent NanoMicrobiology (NAMI), 1050 Brussels, Belgium;
- International Joint Research Group VUB-EPFL NanoBiotechnology & NanoMedicine (NANO), Vrije Universiteit Brussel (VUB), 1050 Brussels, Belgium
- Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland
| | - Bart Devreese
- Alliance Research Group VUB-UGent NanoMicrobiology (NAMI), 1050 Brussels, Belgium;
- International Joint Research Group VUB-EPFL NanoBiotechnology & NanoMedicine (NANO), Vrije Universiteit Brussel (VUB), 1050 Brussels, Belgium
- Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland
- Laboratory for Microbiology, Gent University (UGent), 9000 Gent, Belgium
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8
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Thamban Chandrika N, Dennis EK, Brubaker KR, Kwiatkowski S, Watt DS, Garneau-Tsodikova S. Broad-Spectrum Antifungal Agents: Fluorinated Aryl- and Heteroaryl-Substituted Hydrazones. ChemMedChem 2021; 16:124-133. [PMID: 33063957 PMCID: PMC10898509 DOI: 10.1002/cmdc.202000626] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 09/28/2020] [Indexed: 12/25/2022]
Abstract
Fluorinated aryl- and heteroaryl-substituted monohydrazones displayed excellent broad-spectrum activity against various fungal strains, including a panel of clinically relevant Candida auris strains relative to a control antifungal agent, voriconazole (VRC). These monohydrazones displayed less hemolysis of murine red blood cells than that of VRC at the same concentrations, possessed fungicidal activity in a time-kill study, and exhibited no mammalian cell cytotoxicity. In addition, these monohydrazones prevented the formation of biofilms that otherwise block antibiotic effectiveness and did not trigger the development of resistance when exposed to C. auris AR Bank # 0390 over 15 passages.
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Affiliation(s)
- Nishad Thamban Chandrika
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, 40536-0596, USA
| | - Emily K Dennis
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, 40536-0596, USA
| | - Katelyn R Brubaker
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, 40536-0596, USA
| | - Stefan Kwiatkowski
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, 40536-0596, USA
- Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, Lexington, KY, 40536-0596, USA
| | - David S Watt
- Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, Lexington, KY, 40536-0596, USA
- Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY, 40536-0509, USA
| | - Sylvie Garneau-Tsodikova
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, 40536-0596, USA
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Shaikh MS, Chandrasekaran B, Palkar MB, Kanhed AM, Kajee A, Mlisana KP, Singh P, Ghai M, Cleopus Mahlalela M, Karpoormath R. Synthesis and Biological Evaluation of Novel Carbazole Hybrids as Promising Antimicrobial Agents. Chem Biodivers 2020; 17:e1900550. [PMID: 32149467 DOI: 10.1002/cbdv.201900550] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Accepted: 03/06/2020] [Indexed: 11/10/2022]
Abstract
Two series of carbazole analogs of 8-methoxy-N-substituted-9H-carbazole-3-carboxamides (series 1) and carbazolyl substituted rhodanines (series 2) were synthesized through facile synthetic routes. All the final compounds from these two series were evaluated for their preliminary in vitro antifungal and antibacterial activity against four fungal (Candida albicans, Cryptococcus neoformans, Cryptococcus tropicalis and Aspergillus niger) and four bacterial (Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa) strains, respectively. Among the tested compounds, three compounds of series 1 displayed promising antifungal and antibacterial activity, especially against C. neoformans and S. aureus. In addition, one compound of series 1 displayed notable antimicrobial activity (MIC: 6.25 μg/mL) against clinical isolates of C. albicans and C. neoformans (MIC: 12.5 μg/mL). From the second series, four compounds exhibited significant antifungal and antibacterial activity, especially against C. neoformans and S. aureus. The most active compound of series 2 displayed a prominent antimicrobial activity against C. neoformans (MIC: 3.125 μg/mL) and S. aureus (MIC: 1.56 μg/mL), respectively.
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Affiliation(s)
- Mahamadhanif S Shaikh
- Department of Pharmaceutical Chemistry, Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal (Westville), Durban, 4000, South Africa
| | - Balakumar Chandrasekaran
- Department of Pharmaceutical Chemistry, Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal (Westville), Durban, 4000, South Africa.,Faculty of Pharmacy, Philadelphia University-Jordan, P.O. Box 1, Philadelphia University-19392, Jordan
| | - Mahesh B Palkar
- Department of Pharmaceutical Chemistry, Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal (Westville), Durban, 4000, South Africa
| | - Ashish M Kanhed
- Department of Pharmaceutical Chemistry, Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal (Westville), Durban, 4000, South Africa
| | - Afsana Kajee
- Department of Pharmaceutical Chemistry, Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal (Westville), Durban, 4000, South Africa.,Department of Microbiology, School of Laboratory Medicine and Medical Sciences, National Health Laboratory Services (NHLS), Inkosi Albert Luthuli Central Hospital Academic Complex, University of KwaZulu-Natal, Durban, 4091, South Africa
| | - Koleka P Mlisana
- Department of Microbiology, School of Laboratory Medicine and Medical Sciences, National Health Laboratory Services (NHLS), Inkosi Albert Luthuli Central Hospital Academic Complex, University of KwaZulu-Natal, Durban, 4091, South Africa
| | - Parvesh Singh
- Department of Chemistry, School of Chemistry and Physics, College of Agriculture, Science and Engineering, University of KwaZulu-Natal (Westville), Durban, 4000, South Africa
| | - Meenu Ghai
- Discipline of Genetics, School of Life Sciences, College of Agriculture, Science and Engineering, University of KwaZulu-Natal (Westville), Durban, 4000, South Africa
| | - Mavela Cleopus Mahlalela
- Department of Pharmaceutical Chemistry, Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal (Westville), Durban, 4000, South Africa
| | - Rajshekhar Karpoormath
- Department of Pharmaceutical Chemistry, Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal (Westville), Durban, 4000, South Africa
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Motamedi M, Saharkhiz MJ, Pakshir K, Amini Akbarabadi S, Alikhani Khordshami M, Asadian F, Zareshahrabadi Z, Zomorodian K. Chemical compositions and antifungal activities of Satureja macrosiphon against Candida and Aspergillus species. Curr Med Mycol 2020; 5:20-25. [PMID: 32104740 PMCID: PMC7034783 DOI: 10.18502/cmm.5.4.2162] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
Background and Purpose: Despite the various applications of Satureja species, there are limited data in this domain. Regarding this, the present study was conducted to investigate the essential oil (EO) biological activity of S. macrosiphon species in Iran. Materials and Methods: The EO of S. macrosiphon flowers was obtained by hydrodistillation. Chemical compositions of the EO were analyzed using gas chromatography-mass spectrometry. In addition, minimum inhibitory concentrations (MIC) were measured by means of the broth microdilution method. The estimation of antibiofilm and cytotoxic activities was also accomplished using the tetrazolium salt and MTT assays, respectively. Results: A total of 26 components were identified in the EO with linalool as the main constituent (28.46%). A MIC range value of 0.25-8 μL/mL was obtained against all of the tested fungi. The EO inhibited the biofilm development of the Candida tested strains at a concentration of 4-8 μL/mL. Cytotoxicity (IC50) of EO against the HeLa cell was greater than the MIC concentration (6.49 μL/mL). Conclusion: Based on the findings, it was concluded that the EO of S. macrosiphon has the potential for further use as an antifungal agent.
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Affiliation(s)
- Marjan Motamedi
- Department of Medical Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Keyvan Pakshir
- Department of Medical Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.,Basic Sciences in Infectious Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sara Amini Akbarabadi
- Department of Medical Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Marzieh Alikhani Khordshami
- Department of Medical Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Fatemeh Asadian
- Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zahra Zareshahrabadi
- Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Kamiar Zomorodian
- Department of Medical Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.,Basic Sciences in Infectious Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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11
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Zamani L, Faghih Z, Zomorodian K, Mirjalili BBF, Jalilian A, Khabnadideh S. Nano-SnCl 4.SiO 2, an efficient catalyst for synthesis of benzimidazole drivatives as antifungal and cytotoxic agents. Res Pharm Sci 2019; 14:496-503. [PMID: 32038729 PMCID: PMC6937748 DOI: 10.4103/1735-5362.272536] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
The concept of green chemistry has made significant impact on many frontages including the use of green solvents or sustainable catalyst materials. Benzimidazole ring is an important nitrogen-containing heterocyclic, which exhibits a broad spectrum of bioactivities and are widely utilized by the medicinal chemists for drug discovery. A simple and efficient method was developed for the synthesis of some benzimidazole derivatives via reaction of o-phenylenediamine and substituted aldehydes in the presence of nano-SnCl4/SiO2 as a mild catalyst. Ten 2-substituted benzimidazole compounds ( J1-J10 ) were synthesized. All compounds were evaluated against different species of yeasts and filament fungi using broth micro dilution method as recommended by clinical and laboratory standard institute. Among these compounds, the active ones were chosen for their cytotoxic activities evaluation against MCF-7 and A549 cell lines using MTT method. Compound J2 showed the best antifungal activity against all tested species. Compounds J5-J7 had also desirable antifungal activities. Our cytotoxic results were also similar to the antifungal activities except for J7 which had no cytotoxic activity.
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Affiliation(s)
- Leila Zamani
- Pharmaceutical Sciences Research Centre, Shiraz University of Medical Sciences, Shiraz, I.R. Iran
| | - Zeinab Faghih
- Pharmaceutical Sciences Research Centre, Shiraz University of Medical Sciences, Shiraz, I.R. Iran
| | - Kamiar Zomorodian
- Center of Basic Researches in Infectious Diseases, Department of Medical Mycology, and Parasitology School of Medicine, Shiraz University of Medical Sciences, Shiraz, I.R. Iran
| | | | - Asghar Jalilian
- Pharmaceutical Sciences Research Centre, Shiraz University of Medical Sciences, Shiraz, I.R. Iran
| | - Soghra Khabnadideh
- Pharmaceutical Sciences Research Centre, Shiraz University of Medical Sciences, Shiraz, I.R. Iran
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12
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Assress HA, Selvarajan R, Nyoni H, Ntushelo K, Mamba BB, Msagati TAM. Diversity, Co-occurrence and Implications of Fungal Communities in Wastewater Treatment Plants. Sci Rep 2019; 9:14056. [PMID: 31575971 PMCID: PMC6773715 DOI: 10.1038/s41598-019-50624-z] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Accepted: 09/17/2019] [Indexed: 01/15/2023] Open
Abstract
Three wastewater treatment plants (WWTPs) located in Gauteng province in South Africa were investigated to determine the diversity, co-occurrence and implications of their fungal communities using illumina sequencing platform and network analysis. Phylogenetic taxonomy revealed that members of the fungal communities were assigned to 6 phyla and 361 genera. Basidiomycota and Ascomycota were the most abundant phyla, dominated by the genera Naumovozyma, Pseudotomentella, Derxomyces, Ophiocordyceps, Pulchromyces and Paecilomyces. Phylogenetic analysis revealed the existence of fungal OTUs related to class lineages such as Agaricomycetes, Eurotiomycetes and Sordariomycetes indicating new fungal diversity in WWTPs. Dominant and rare fungal genera that can potentially be used in bioremediation such as Trichoderma, Acremonium, Talaromyces, Paecilomyces, cladophialophora and Saccharomyces were detected. Conversely, genera whose members are known to be pathogenic to human and plant such as Olpidium, Paecilomyces, Aspergillus, Rhodotorula, Penicillium, Candida, Synchytrium, Phyllosticta and Mucor were also detected in all WWTPs. Phylotype analysis confirmed that some fungal phylotypes were highly similar to the reported fungal pathogens of concern. Co-occurrence network analysis revealed that the fungal genera such as Minimedusa, Glomus, Circinella, Coltricia, Caloplaca, Phylosticta, Peziza, Candida, and Hydnobolites were the major networking hub in the WWTPs. The overall results in this study highlighted that WWTPs represent a potential source of beneficial fungi for bioremediation of pollutants in the ecosystem and the need to consider human and plant fungal pathogens during safety evaluation of treated wastewater for reuse.
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Affiliation(s)
- Hailemariam Abrha Assress
- University of South Africa, College of Science Engineering and Technology, Nanotechnology and Water Sustainability Research Unit, UNISA Science Campus, Florida, 1709, Johannesburg, South Africa
| | - Ramganesh Selvarajan
- University of South Africa, College of Agriculture and Environmental sciences, UNISA Science Florida, 1709, Johannesburg, South Africa
| | - Hlengilizwe Nyoni
- University of South Africa, College of Science Engineering and Technology, Nanotechnology and Water Sustainability Research Unit, UNISA Science Campus, Florida, 1709, Johannesburg, South Africa
| | - Khayalethu Ntushelo
- University of South Africa, College of Agriculture and Environmental sciences, UNISA Science Florida, 1709, Johannesburg, South Africa
| | - Bhekie B Mamba
- University of South Africa, College of Science Engineering and Technology, Nanotechnology and Water Sustainability Research Unit, UNISA Science Campus, Florida, 1709, Johannesburg, South Africa.,State Key Laboratory of Seperation and Membranes, Membrane Processes, National Center for International Joint Research on Membrane Science and Technologya, Tianjing, 300387, People's Republic of China
| | - Titus A M Msagati
- University of South Africa, College of Science Engineering and Technology, Nanotechnology and Water Sustainability Research Unit, UNISA Science Campus, Florida, 1709, Johannesburg, South Africa.
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13
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Özenci V, Klingspor L, Ullberg M, Chryssanthou E, Denning DW, Kondori N. Estimated burden of fungal infections in Sweden. Mycoses 2019; 62:1043-1048. [PMID: 31376228 DOI: 10.1111/myc.12981] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/30/2019] [Indexed: 11/29/2022]
Abstract
The aim of this study was to estimate the annual burden of fungal infections in Sweden using data mainly from 2016. Data on specific populations were obtained from Swedish national data registries. Annual incidence and prevalence of fungal disease was calculated based on epidemiological studies. Data on infections due to Cryptococcus sp., Mucorales, Histoplasma capsulatum, Coccidioides immitis and Pneumocystis jirovecii were retrieved from Karolinska University Laboratory and covers only 25% of Swedish population. In 2016, the population of Sweden was 9 995 153 (49.8% female). The overall burden of fungal infections was 1 713 385 (17 142/100 000). Superficial fungal infections affect 1 429 307 people (1429/100 000) based on Global Burden of Disease 14.3% prevalence. Total serious fungal infection burden was 284 174 (2843/100 000) in 2016. Recurrent Candida vulvovaginitis is common; assuming a 6% prevalence in women. Prevalence of allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitisation were estimated to be 20 095 and 26 387, respectively. Similarly, chronic pulmonary aspergillosis was estimated to affect 490 patients after tuberculosis, sarcoidosis and other conditions. Candidemia incidence was estimated to be 500 in 2016 (4.7/100 000) and invasive aspergillosis 295 (3.0/100 000). In Stockholm area, Mucorales were reported in three patients in 2015, while Cryptococcus spp. were reported in two patients. In 2016, there were 297 patients PCR positive for P jirovecii. The present study shows that the overall burden of fungal infections in Sweden is high and affects 17% of the population. The morbidity, mortality and the healthcare-related costs due to fungal infections warrant further studies.
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Affiliation(s)
- Volkan Özenci
- Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.,Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden
| | - Lena Klingspor
- Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Måns Ullberg
- Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden
| | - Erja Chryssanthou
- Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.,Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden
| | - David W Denning
- National Aspergillosis Centre, Wythenshawe Hospital, The University of Manchester, Manchester, UK
| | - Nahid Kondori
- Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Clinical Microbiology, Sahlgrenska University Hospital, Gothenburg, Sweden
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14
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Chen Y, Zhang Y, Ye H, Dou Y, Lu D, Li X, Limper AH, Han J, Su D. Structural basis for the acetylation of histone H3K9 and H3K27 mediated by the histone chaperone Vps75 in Pneumocystis carinii. Signal Transduct Target Ther 2019; 4:14. [PMID: 31098304 PMCID: PMC6509256 DOI: 10.1038/s41392-019-0047-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2019] [Accepted: 03/26/2019] [Indexed: 02/05/2023] Open
Abstract
Rtt109 is a histone acetyltransferase (HAT) that is a potential therapeutic target in conditioned pathogenic fungi Pneumocystis carinii (P. carinii). The histone chaperone Vps75 can stimulate the Rtt109-dependent acetylation of several histone H3 lysines and preferentially acetylates H3K9 and H3K27 within canonical histone (H3-H4)2 tetramers. Vps75 shows two protein conformations assembled into dimeric and tetrameric forms, but the roles played by multimeric forms of Vps75 in Rtt109-mediated histone acetylation remain elusive. In P. carinii, we identified that Vps75 (PcVps75) dimers regulate H3K9 and H3K27 acetylation by directly interacting with histone (H3-H4)2 tetramers, rather than by forming a Vps75-Rtt109 complex. For PcVps75 tetramers, the major histone-binding surface is buried within a walnut-like structure in the absence of a histone cargo. Based on crystal structures of dimeric and tetrameric forms of PcVps75, as well as HAT assay data, we confirmed that residues 192E, 193D, 194E, 195E, and 196E and the disordered C-terminal tail (residues 224-250) of PcVps75 mediate interactions with histones and are important for the Rtt109 in P. carinii (PcRtt109)-mediated acetylation of H3K9 and H3K27, both in vitro and in yeast cells. Furthermore, expressing PcRtt109 alone or in combination with PcVps75 variants that cannot effectively bind histones could not fully restore cellular growth in the presence of genotoxic agents that block DNA replication owing to the absence of H3K9 and H3K27 acetylation. Together, these data indicate that the interaction between PcVps75 and histone (H3-H4)2 tetramers is a critical regulator of the Rtt109-mediated acetylation of H3K9 and H3K27.
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Affiliation(s)
- Yiping Chen
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan P. R. China
| | - Yang Zhang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan P. R. China
| | - Hui Ye
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan P. R. China
| | - Yanshu Dou
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan P. R. China
| | - Deren Lu
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan P. R. China
| | - Xiaolu Li
- International Center for Translational Chinese Medicine, Sichuan Academy of Chinese Medicine Sciences, P.R. China, Chengdu, Sichuan P. R. China
| | - Andrew H. Limper
- Thoracic Diseases Research Unit, Mayo Clinic College of Medicine, Rochester, MN USA
| | - Junhong Han
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan P. R. China
| | - Dan Su
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan P. R. China
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15
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N-haloacetyl phenothiazines and derivatives: Preparation, characterization and structure-activity relationship for antifungal activity. ARAB J CHEM 2019. [DOI: 10.1016/j.arabjc.2017.11.019] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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16
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Antifungal Susceptibility Profiles of Candida Species Isolated from Ahvaz Jundishapur Educational Hospitals. Jundishapur J Microbiol 2018. [DOI: 10.5812/jjm.78851] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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17
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18
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Synthesis and Anticandidal Activity of New Imidazole-Chalcones. Molecules 2018; 23:molecules23040831. [PMID: 29617329 PMCID: PMC6017838 DOI: 10.3390/molecules23040831] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2018] [Revised: 03/28/2018] [Accepted: 03/29/2018] [Indexed: 11/16/2022] Open
Abstract
In the present work, 15 new 1-(4-(1H-imidazol-1-yl)phenyl)-3-(4-substituedphenyl)prop-2-en-1-one derivatives (3a–3o) were synthesized to evaluate their antifungal activity. Structures of newly synthesized imidazole derivatives (3a–3o) were characterized by IR, 1H-NMR, 13C-NMR, and LCMSMS spectroscopic methods. The anticandidal activity of compounds (3a–3o) against C. albicans (ATCC 24433), C. krusei (ATCC 6258), C. parapsilosis (ATCC 22019), and C. glabrata (ATCC 90030) was elucidated according to the EUCAST definitive (EDef 7.1) method. Consistent with the activity studies, 3a–3d were found to be more potent derivatives with their MIC50 values (0.78 µg/mL–3.125 µg/mL) against Candida strains. Compound 3c indicated similar antifungal activity to ketoconazole against all Candida species and was evaluated as the most active derivative in the series. Effects of the most potent derivatives 3a–3d on ergosterol biosynthesis were observed by LC-MS-MS method, which is based on quantification of the ergosterol level in C. krusei. Moreover, these compounds were subjected to a cytotoxicity test for the preliminary toxicological profiles and were found as non-cytotoxic. Furthermore, docking studies for the most active derivative 3c were performed to evaluate its binding modes on lanosterol 14-α-demethylase. In addition to in vitro tests, docking studies also revealed that Compound 3c is a potential ergosterol biosynthesis inhibitor.
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Ala-Houhala M, Koukila-Kähkölä P, Antikainen J, Valve J, Kirveskari J, Anttila VJ. Clinical use of fungal PCR from deep tissue samples in the diagnosis of invasive fungal diseases: a retrospective observational study. Clin Microbiol Infect 2018; 24:301-305. [PMID: 28870728 DOI: 10.1016/j.cmi.2017.08.017] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Revised: 08/19/2017] [Accepted: 08/23/2017] [Indexed: 10/18/2022]
Abstract
OBJECTIVES To assess the clinical use of panfungal PCR for diagnosis of invasive fungal diseases (IFDs). We focused on the deep tissue samples. METHODS We first described the design of panfungal PCR, which is in clinical use at Helsinki University Hospital. Next we retrospectively evaluated the results of 307 fungal PCR tests performed from 2013 to 2015. Samples were taken from normally sterile tissues and fluids. The patient population was nonselected. We classified the likelihood of IFD according to the criteria of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG), comparing the fungal PCR results to the likelihood of IFD along with culture and microscopy results. RESULTS There were 48 positive (16%) and 259 negative (84%) PCR results. The sensitivity and specificity of PCR for diagnosing IFDs were 60.5% and 91.7%, respectively, while the negative predictive value and positive predictive value were 93.4% and 54.2%, respectively. The concordance between the PCR and the culture results was 86% and 87% between PCR and microscopy, respectively. Of the 48 patients with positive PCR results, 23 had a proven or probable IFD. CONCLUSIONS Fungal PCR can be useful for diagnosing IFDs in deep tissue samples. It is beneficial to combine fungal PCR with culture and microscopy.
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Affiliation(s)
- M Ala-Houhala
- Inflammation Center, Division of Infectious Diseases, Helsinki University Hospital and University of Helsinki, Finland
| | | | - J Antikainen
- Helsinki University Hospital Laboratory, Helsinki, Finland
| | - J Valve
- Helsinki University Hospital Laboratory, Helsinki, Finland
| | - J Kirveskari
- Helsinki University Hospital Laboratory, Helsinki, Finland
| | - V-J Anttila
- Inflammation Center, Division of Infectious Diseases, Helsinki University Hospital and University of Helsinki, Finland.
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20
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Czurda S, Lion T. Broad-Spectrum Molecular Detection of Fungal Nucleic Acids by PCR-Based Amplification Techniques. Methods Mol Biol 2018; 1508:257-266. [PMID: 27837509 DOI: 10.1007/978-1-4939-6515-1_14] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Abstract
Over the past decade, the incidence of life-threatening invasive fungal infections has dramatically increased. Infections caused by hitherto rare and emerging fungal pathogens are associated with significant morbidity and mortality among immunocompromised patients. These observations render the coverage of a broad range of clinically relevant fungal pathogens highly important. The so-called panfungal or, perhaps more correctly, broad-range nucleic acid amplification techniques do not only facilitate sensitive detection of all clinically relevant fungal species but are also rapid and can be applied to analyses of any patient specimens. They have therefore become valuable diagnostic tools for sensitive screening of patients at risk of invasive fungal infections. This chapter summarizes the currently available molecular technologies employed in testing of a wide range of fungal pathogens, and provides a detailed workflow for patient screening by broad-spectrum nucleic acid amplification techniques.
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Affiliation(s)
- Stefan Czurda
- Children's Cancer Research Institute (CCRI), St. Anna Kinderkrebsforschung, Vienna, Austria.,LabDia Labordiagnostik GmbH, Vienna, Austria
| | - Thomas Lion
- Children's Cancer Research Institute (CCRI), St. Anna Kinderkrebsforschung, Vienna, Austria. .,LabDia Labordiagnostik GmbH, Vienna, Austria. .,Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
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21
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Raab P, Sedlacek L, Buchholz S, Stolle S, Lanfermann H. Imaging Patterns of Rhino-Orbital-Cerebral Mucormycosis in Immunocompromised Patients : When to Suspect Complicated Mucormycosis. Clin Neuroradiol 2017; 27:469-475. [PMID: 29026931 DOI: 10.1007/s00062-017-0629-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Accepted: 09/14/2017] [Indexed: 10/18/2022]
Abstract
PURPOSE The aim of this study was to describe radiological imaging findings of a complicated sinusitis, which should raise the suspicion of rhino-orbital-cerebral mucormycosis as being the underlying cause. METHODS In this retrospective analysis, we describe the cases and imaging findings of 8 patients with proven mucormycosis. These patients presented mostly with new facial or orbital swelling and were referred for imaging to our institution. Magnetic resonance imaging and computed tomography images were classified as abnormal or normal with respect to orbital, paranasal and cerebral signal results. Special emphasis was placed on the distribution of the signal abnormalities regarding involvement of the skull base and the cavernous sinus. RESULTS Out of a pool of 43 patients with colonization or proven Mucorales infection at different sites of the body, we identified 8 patients with infiltration of the midface and skull base. Unexpectedly seven out of the eight patients with abnormal findings of the paranasal sinuses and the adjacent tissues showed no bony sinus wall destruction. Of the eight patients seven showed inflammatory changes involving the infratemporal fossa and facial/periorbital tissues, three of the eight patients suffered from fungal invasion of the cavernous sinus and the carotid artery and one of the eight patients had a local infection of the hard palate only. CONCLUSION Imaging findings of inflammatory tissue infiltration adjacent to the paranasal sinuses with possible extension into the pterygopalatine fossa, infratemporal fossa and orbit or the cavernous sinus should raise the suspicion of a mucormycosis, especially in immunocompromised patients.
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Affiliation(s)
- Peter Raab
- Institute of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
| | - Ludwig Sedlacek
- Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
| | - Stefanie Buchholz
- Praxis Dr. Buchholz, Goslarsche Str. 14, 38304, Wolfenbüttel, Germany
| | - Stefan Stolle
- Department of ENT, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
| | - H Lanfermann
- Institute of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
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22
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Arbefeville S, Harris A, Ferrieri P. Comparison of sequencing the D2 region of the large subunit ribosomal RNA gene (MicroSEQ®) versus the internal transcribed spacer (ITS) regions using two public databases for identification of common and uncommon clinically relevant fungal species. J Microbiol Methods 2017. [PMID: 28647582 DOI: 10.1016/j.mimet.2017.06.015] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
CONTEXT Fungal infections cause considerable morbidity and mortality in immunocompromised patients. Rapid and accurate identification of fungi is essential to guide accurately targeted antifungal therapy. With the advent of molecular methods, clinical laboratories can use new technologies to supplement traditional phenotypic identification of fungi. OBJECTIVE The aims of the study were to evaluate the sole commercially available MicroSEQ® D2 LSU rDNA Fungal Identification Kit compared to the in-house developed internal transcribed spacer (ITS) regions assay in identifying moulds, using two well-known online public databases to analyze sequenced data. DESIGN 85 common and uncommon clinically relevant fungi isolated from clinical specimens were sequenced for the D2 region of the large subunit (LSU) of ribosomal RNA (rRNA) gene with the MicroSEQ® Kit and the ITS regions with the in house developed assay. The generated sequenced data were analyzed with the online GenBank and MycoBank public databases. RESULTS The D2 region of the LSU rRNA gene identified 89.4% or 92.9% of the 85 isolates to the genus level and the full ITS region (f-ITS) 96.5% or 100%, using GenBank or MycoBank, respectively, when compared to the consensus ID. When comparing species-level designations to the consensus ID, D2 region of the LSU rRNA gene aligned with 44.7% (38/85) or 52.9% (45/85) of these isolates in GenBank or MycoBank, respectively. By comparison, f-ITS possessed greater specificity, followed by ITS1, then ITS2 regions using GenBank or MycoBank. Using GenBank or MycoBank, D2 region of the LSU rRNA gene outperformed phenotypic based ID at the genus level. Comparing rates of ID between D2 region of the LSU rRNA gene and the ITS regions in GenBank or MycoBank at the species level against the consensus ID, f-ITS and ITS2 exceeded performance of the D2 region of the LSU rRNA gene, but ITS1 had similar performance to the D2 region of the LSU rRNA gene using MycoBank. CONCLUSION Our results indicated that the MicroSEQ® D2 LSU rDNA Fungal Identification Kit was equivalent to the in-house developed ITS regions assay to identify fungi at the genus level. The MycoBank database gave a better curated database and thus allowed a better genus and species identification for both D2 region of the LSU rRNA gene and ITS regions.
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Affiliation(s)
- S Arbefeville
- Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, MMC 609 Mayo, 420 Delaware St. S.E., Minneapolis, MN 55455, USA.
| | - A Harris
- Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, MMC 609 Mayo, 420 Delaware St. S.E., Minneapolis, MN 55455, USA
| | - P Ferrieri
- Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, MMC 609 Mayo, 420 Delaware St. S.E., Minneapolis, MN 55455, USA
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Sweileh WM, Sawalha AF, Al-Jabi S, Zyoud SH. Bibliometric analysis of literature on antifungal triazole resistance: 1980 - 2015. Germs 2017; 7:19-27. [PMID: 28331838 PMCID: PMC5348213 DOI: 10.18683/germs.2017.1104] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Revised: 02/04/2017] [Accepted: 02/06/2016] [Indexed: 02/05/2023]
Abstract
BACKGROUND Triazole antifungal agents play an important role in the treatment of a wide range of fungal infections. Little is known about antifungal triazole drug resistance when compared to antibiotic resistance. Therefore, this study was carried out to give a bibliometric overview of literature on triazole antifungal drug resistance. METHODS Keywords related to triazole drug class and resistance were used in a search query in the Scopus search engine. The time span was set from 1980 to 2015. Data pertaining to growth of publications, the most active countries and institutions, the most cited articles, and mapping of molecular mechanisms of resistance were analyzed. RESULTS A total of 1648 journal articles were retrieved with an average of 20.46 citations per article. Annual growth of triazole resistance showed an increasing pattern during the study period. The United States of America (n=446; 27.06%) ranked first in productivity followed by the United Kingdom (UK) (n=176; 10.68%), and China (n=133; 8.07%). Radboud University Nijmegen Medical Centre (n=69, 4.19%) in the Netherlands ranked first in productivity, while the journal Antimicrobial Agents and Chemotherapy ranked first (n=255; 15.47%) in publishing articles on triazole resistance. Mapping mechanisms of resistance showed that efflux pump and mutations in target enzyme are major mechanisms described in resistance to triazoles. CONCLUSION There was a growth of publications on triazole resistance in the past two decades with the bulk of publications on triazole resistance in Candida species. The data presented here will serve as baseline information for future comparative purposes.
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Affiliation(s)
- Waleed M. Sweileh
- PhD, Professor, Department of Physiology, Pharmacology and Toxicology, College of Medicine and Health Sciences, An-Najah National University, P.O. Box 7, Nablus, Palestine
| | - Ansam F. Sawalha
- PhD, Professor, Department of Physiology, Pharmacology and Toxicology, College of Medicine and Health Sciences, An-Najah National University, P.O. Box 7, Nablus, Palestine
- Corresponding Author: Ansam F. Sawalha, PhD, Professor, Department of Physiology, Pharmacology and Toxicology, College of Medicine and Health Sciences, An-Najah National University, P.O. Box 7, Nablus, Palestine.
| | - Samah Al-Jabi
- PhD, Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, P.O. Box 7, Nablus, Palestine
| | - Sa’ed H. Zyoud
- PhD, Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, P.O. Box 7, Nablus, Palestine
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Synthesis, X-ray Single Crystal Structure, Molecular Docking and DFT Computations on N-[(1E)-1-(2H-1,3-Benzodioxol-5-yl)-3-(1H-imidazol-1-yl)propylidene]-hydroxylamine: A New Potential Antifungal Agent Precursor. Molecules 2017; 22:molecules22030373. [PMID: 28264518 PMCID: PMC6155236 DOI: 10.3390/molecules22030373] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Revised: 02/12/2017] [Accepted: 02/21/2017] [Indexed: 11/17/2022] Open
Abstract
Mycoses are serious health problem, especially in immunocompromised individuals. A new imidazole-bearing compound containing an oxime functionality was synthesized and characterized with different spectroscopic techniques to be used for the preparation of new antifungal agents. The stereochemistry of the oxime double bond was unequivocally determined via the single crystal X-ray technique. The title compound 4, C13H13N3O3·C3H8O, crystallizes in the monoclinic space group P21with a = 9.0963(3) Å, b = 14.7244(6) Å, c = 10.7035(4) Å, β = 94.298 (3)°, V = 1429.57(9) Å3, Z = 2. The molecules were packed in the crystal structure by eight intermolecular hydrogen bond interactions. A comprehensive spectral analysis of the title molecule 4 has been performed based on the scaled quantum mechanical (SQM) force field obtained by density-functional theory (DFT) calculations. A molecular docking study illustrated the binding mode of the title compound 4 into its target protein. The preliminary antifungal activity of the title compound 4 was determined using a broth microdilution assay.
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A Rare Diagnosis: Recognizing and Managing Fungal Tenosynovitis of the Hand and Upper Extremity. J Hand Surg Am 2017; 42:e77-e89. [PMID: 28011032 DOI: 10.1016/j.jhsa.2016.11.014] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2016] [Revised: 10/31/2016] [Accepted: 11/08/2016] [Indexed: 02/02/2023]
Abstract
PURPOSE Fungal infections involving the tenosynovium of the upper extremity are uncommon and are often misdiagnosed. This study evaluates the epidemiology, diagnosis, treatment, and outcomes of patients with fungal tenosynovitis of the upper extremity over a 20-year period. METHODS A retrospective review of all culture-confirmed cases of fungal tenosynovitis of the upper extremity treated between 1990 and 2013 at a single institution was performed. Clinical data included patient and epidemiologic risk factors, causative fungal organism, surgical management, antimicrobial regimen, recurrence rates, and outcomes. RESULTS There were 10 patients (9 female, 1 male) who met the inclusion criteria. The mean patient age was 60 years (range, 47-76 y). Identified pathogens included Histoplasmacapsulatum (7), Coccidioides posadasii/immitis (2), and Cryptococcus neoformans (1). Eight patients were on immunosuppressant medications at the time of diagnosis. The most common clinical presentation was subacute localized pain, swelling, and erythema consistent with tenosynovitis. The diagnosis was delayed by a median of 6 months (range, 0-48 mo). The most helpful diagnostic imaging studies included magnetic resonance imaging and ultrasound. All patients were treated with extensive surgical synovectomy and debridement. Seven patients were treated by a single surgery, whereas 3 required multiple consecutive debridements (2, 7, and 10 surgeries). The mean course of initial antimicrobial therapy was 8.2 months (range, 3-12 mo). Clinical recurrence was noted in 3 patients (30%) during a median follow-up period of 46 months (range, 7-250 mo). Both patients with Coccidioides infection incurred recurrence. CONCLUSIONS Although uncommon, surgeons and clinicians should consider a diagnosis of fungal tenosynovitis among immunocompromised patients with signs of mild tenosynovitis and should consider operative debridement and biopsy. Although the majority of patients were successfully treated with surgical debridement and antimicrobial therapy, a recurrence rate of 30% highlights the need for close post-treatment follow-up. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic V.
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26
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Tong X, Xu H, Zou L, Cai M, Xu X, Zhao Z, Xiao F, Li Y. High diversity of airborne fungi in the hospital environment as revealed by meta-sequencing-based microbiome analysis. Sci Rep 2017; 7:39606. [PMID: 28045065 PMCID: PMC5206710 DOI: 10.1038/srep39606] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2016] [Accepted: 11/24/2016] [Indexed: 12/28/2022] Open
Abstract
Invasive fungal infections acquired in the hospital have progressively emerged as an important cause of life-threatening infection. In particular, airborne fungi in hospitals are considered critical pathogens of hospital-associated infections. To identify the causative airborne microorganisms, high-volume air samplers were utilized for collection, and species identification was performed using a culture-based method and DNA sequencing analysis with the Illumina MiSeq and HiSeq 2000 sequencing systems. Few bacteria were grown after cultivation in blood agar. However, using microbiome sequencing, the relative abundance of fungi, Archaea species, bacteria and viruses was determined. The distribution characteristics of fungi were investigated using heat map analysis of four departments, including the Respiratory Intensive Care Unit, Intensive Care Unit, Emergency Room and Outpatient Department. The prevalence of Aspergillus among fungi was the highest at the species level, approximately 17% to 61%, and the prevalence of Aspergillus fumigatus among Aspergillus species was from 34% to 50% in the four departments. Draft genomes of microorganisms isolated from the hospital environment were obtained by sequence analysis, indicating that investigation into the diversity of airborne fungi may provide reliable results for hospital infection control and surveillance.
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Affiliation(s)
- Xunliang Tong
- Department of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, The People's Republic of China
| | - Hongtao Xu
- Department of Laboratory Medicine, Beijing Hospital, Beijing, The People's Republic of China
| | - Lihui Zou
- Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, Beijing, The People's Republic of China
| | - Meng Cai
- Department of Hospital Infection Control and Management, Beijing Hospital, Beijing, The People's Republic of China
| | - Xuefeng Xu
- National Clinical Research Centre for Respiratory Medicine, Beijing Hospital, Beijing, The People's Republic of China
| | - Zuotao Zhao
- Department of Dermatology, First Hospital, Peking University, Beijing, The People's Republic of China
| | - Fei Xiao
- Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, Beijing, The People's Republic of China
| | - Yanming Li
- Department of Hospital Infection Control and Management, Beijing Hospital, Beijing, The People's Republic of China.,Department of Respiratory and Critical Care Medicine, Beijing Hospital, National Center of Respiratory, Beijing, The People's Republic of China
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Barbosa GM, Dos Santos EG, Capella FNC, Homsani F, de Pointis Marçal C, Dos Santos Valle R, de Araújo Abi-Chacra É, Braga-Silva LA, de Oliveira Sales MH, da Silva Neto ID, da Veiga VF, Dos Santos ALS, Holandino C. Direct electric current modifies important cellular aspects and ultrastructure features of Candida albicans yeasts: Influence of doses and polarities. Bioelectromagnetics 2016; 38:95-108. [PMID: 27783424 DOI: 10.1002/bem.22015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2015] [Accepted: 10/07/2016] [Indexed: 11/09/2022]
Abstract
Available treatments against human fungal pathogens present high levels of resistance, motivating the development of new antifungal therapies. In this context, the present work aimed to analyze direct electric current (DC) antifungal action, using an in vitro apparatus equipped with platinum electrodes. Candida albicans yeast cells were submitted to three distinct conditions of DC treatment (anodic flow-AF; electroionic flow-EIF; and cathodic flow-CF), as well as different charges, ranging from 0.03 to 2.40 C. Our results indicated C. albicans presented distinct sensibility depending on the DC intensity and polarity applied. Both the colony-forming unit assay and the cytometry flow with propidium iodide indicated a drastic reduction on cellular viability after AF treatment with 0.15 C, while CF- and EIF-treated cells stayed alive when DC doses were increased up to 2.40 C. Additionally, transmission electron microscopy revealed important ultrastructural alterations in AF-treated yeasts, including cell structure disorganization, ruptures in plasmatic membrane, and cytoplasmic rarefaction. This work emphasizes the importance of physical parameters (polarity and doses) in cellular damage, and brings new evidence for using electrotherapy to treat C. albicans pathology process. Bioelectromagnetics. 38:95-108, 2017. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Gleyce Moreno Barbosa
- Multidisciplinary Laboratory of Pharmaceutical Sciences, Pharmacy College, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Eldio Gonçalves Dos Santos
- Multidisciplinary Laboratory of Pharmaceutical Sciences, Pharmacy College, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Francielle Neves Carvalho Capella
- Multidisciplinary Laboratory of Pharmaceutical Sciences, Pharmacy College, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Fortune Homsani
- Multidisciplinary Laboratory of Pharmaceutical Sciences, Pharmacy College, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Carina de Pointis Marçal
- Peptidases Research Laboratory, Paulo de Góes Microbiology Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Roberta Dos Santos Valle
- Peptidases Research Laboratory, Paulo de Góes Microbiology Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Érika de Araújo Abi-Chacra
- Peptidases Research Laboratory, Paulo de Góes Microbiology Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Lys Adriana Braga-Silva
- Peptidases Research Laboratory, Paulo de Góes Microbiology Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | | | | | - Venicio Feo da Veiga
- Microscopy Sector of Paulo de Góes Microbiology Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - André Luis Souza Dos Santos
- Peptidases Research Laboratory, Paulo de Góes Microbiology Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Carla Holandino
- Multidisciplinary Laboratory of Pharmaceutical Sciences, Pharmacy College, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
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Osmanov A, Denning DW. Burden of serious fungal infections in Ukraine. Mycoses 2016; 58 Suppl 5:94-100. [PMID: 26449513 DOI: 10.1111/myc.12409] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Revised: 08/20/2015] [Accepted: 08/21/2015] [Indexed: 01/12/2023]
Abstract
Ukraine has high rates of TB, AIDS and cancer. We estimated the burden of fungal disease from epidemiology papers and specific populations at risk and fungal infection frequencies. HIV/AIDS cases and deaths (2012) and tuberculosis statistics were obtained from the State Service of Ukraine, while chronic obstructive pulmonary disease (COPD) cases were from M. Miravitlles et al., Thorax 64, 863-868 (2009). Annual estimates are 893,579 Ukrainian women get recurrent vaginal thrush (≥4× per year), 50,847 cases of oral candidiasis and 13,727 cases of oesophageal candidiasis in HIV, and 101 (1%) of 10,085 new AIDS cases develop cryptococcal meningitis, 6152 cases of Pneumocystis pneumonia (13.5 cases per 100,000). Of the 29,265 cases of active respiratory TB in 2012, it is estimated that 2881 new cases of chronic pulmonary aspergillosis (CPA) occurred and that the 5-year period prevalence is 7724 cases with a total CPA burden of 10,054 cases. Assuming adult asthma prevalence is ~2.9%, 28,447 patients with allergic bronchopulmonary aspergillosis (ABPA) are likely and 37,491 with severe asthma with fungal sensitisation. We estimate 2278 cases and 376 postsurgical intra-abdominal Candida infections. Invasive aspergillosis in immunocompromised patients is estimated at 303 patients annually; 930 cases in COPD patients. Ninety cases of mucormycosis (2 per 1,000,000) are estimated. In total, ~1,000,000 (2.2%) people in Ukraine develop serious fungal infections annually.
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Affiliation(s)
- Ali Osmanov
- The University of Manchester, Manchester, UK
| | - David W Denning
- The University of Manchester, Manchester, UK.,Manchester Academic Health Science Centre and National Aspergillosis Centre, University Hospital of South Manchester, Manchester, UK
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29
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Abstract
We are presenting a quantitative proteomics tally of the most commonly expressed conserved fungal proteins of the cytosol, the cell wall, and the secretome. It was our goal to identify fungi-typical proteins that do not share significant homology with human proteins. Such fungal proteins are of interest to the development of vaccines or drug targets. Protein samples were derived from 13 fungal species, cultured in rich or in minimal media; these included clinical isolates of Aspergillus, Candida, Mucor, Cryptococcus, and Coccidioides species. Proteomes were analyzed by quantitative MSE (Mass Spectrometry-Elevated Collision Energy). Several thousand proteins were identified and quantified in total across all fractions and culture conditions. The 42 most abundant proteins identified in fungal cell walls or supernatants shared no to very little homology with human proteins. In contrast, all but five of the 50 most abundant cytosolic proteins had human homologs with sequence identity averaging 59%. Proteomic comparisons of the secreted or surface localized fungal proteins highlighted conserved homologs of the Aspergillus fumigatus proteins 1,3-β-glucanosyltransferases (Bgt1, Gel1-4), Crf1, Ecm33, EglC, and others. The fact that Crf1 and Gel1 were previously shown to be promising vaccine candidates, underlines the value of the proteomics data presented here.
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30
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Design, synthesis and biological evaluation of novel non-azole derivatives as potential antifungal agents. CHINESE CHEM LETT 2015. [DOI: 10.1016/j.cclet.2015.04.030] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
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31
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Antifungal Properties of Crude Extracts, Fractions, and Purified Compounds from Bark of Curatella americana L. (Dilleniaceae) against Candida Species. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2015; 2015:673962. [PMID: 26347790 PMCID: PMC4548135 DOI: 10.1155/2015/673962] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/03/2015] [Revised: 07/02/2015] [Accepted: 07/21/2015] [Indexed: 01/09/2023]
Abstract
The ethnomedicinal plant Curatella americana L. (Dilleniaceae) is a common shrub in the Brazilian cerrado, in which crude extract showed antifungal activity in a preliminary study. In this work, the antifungal and cytotoxic properties of the crude extract, fractions, and isolated compounds from C. americana were evaluated against the standard yeast strains Candida albicans, C. tropicalis, and C. parapsilosis, clinical isolates, and fluconazole-resistant strains. The combinatory effects between subfractions and isolated compounds and effects on cell morphology, virulence factors, and exogenous ergosterol were also evaluated. The MIC obtained against the Candida species including fluconazole-resistant strain ranged from 15.3 to 31.3 µg/mL for crude extract, 3.9 to 15.6 µg/mL for ethyl acetate fraction, and 7.8 to 31.3 µg/mL for subfractions. The isolated compounds identified as 4′-O-methyl-catechin, epicatechin-3-O-gallate, and 4′-O-methyl-catechin-3-O-gallate showed lower antifungal activity than the crude extract and fractions (MIC ranging from 31.3 to 125.0 µg/mL). The addition of exogenous ergosterol to yeast culture did not interfere in the antifungal activity of the extract and its fractions. Synergistic antifungal activity was observed between subfractions and isolated compounds. The effects on virulence factors and the different mechanisms of action compared to fluconazole and nystatin suggest that this ethnomedicinal plant may be an effective alternative treatment for candidiasis.
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Detection of tropical fungi in formalin-fixed, paraffin-embedded tissue: still an indication for microscopy in times of sequence-based diagnosis? BIOMED RESEARCH INTERNATIONAL 2015; 2015:938721. [PMID: 25961048 PMCID: PMC4417575 DOI: 10.1155/2015/938721] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/21/2014] [Revised: 02/27/2015] [Accepted: 03/09/2015] [Indexed: 01/31/2023]
Abstract
INTRODUCTION The aim of the study was the evaluation of panfungal PCR protocols with subsequent sequence analysis for the diagnostic identification of invasive mycoses in formalin-fixed, paraffin-embedded tissue samples with rare tropical mycoses. MATERIALS AND METHODS Five different previously described panfungal PCR/sequencing protocols targeting 18S and 28S ribosomal RNA gene fragments as well as internal transcribed spacer 1 and 2 fragments were evaluated with a collection of 17 formalin-fixed, paraffin-embedded tissue samples of patients with rare and/or tropical invasive mycoses, comprising chromoblastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, mucormycosis, mycetoma/maduromycosis, and rhinosporidiosis, in a proof-of-principle analysis. RESULTS The primers of the panfungal PCRs readily and predominantly reacted with contaminating environmental fungi that had deposited on the paraffin blocks. Altogether three sequence results of histoplasmosis and mycetoma samples that matched the histological assessment were associated with sample age <10 years and virtually without PCR inhibition. CONCLUSIONS The high risk of amplifying environmental contaminants severely reduces the usefulness of the assessed panfungal PCR/sequencing protocols for the identification of rare and/or tropical mycoses in stored formalin-fixed, paraffin-embedded tissues. Histological assessment remains valuable for such indications if cultural differentiation is impossible from inactivated sample material.
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Elhoufi A, Ahmadi A, Asnaashari AMH, Davarpanah MA, Bidgoli BF, Moghaddam OM, Torabi-Nami M, Abbasi S, El-Sobky M, Ghaziani A, Jarrahzadeh MH, Shahrami R, Shirazian F, Soltani F, Yazdinejad H, Zand F. Invasive candidiasis in critical care setting, updated recommendations from “Invasive Fungal Infections-Clinical Forum”, Iran. World J Crit Care Med 2014; 3:102-112. [PMID: 25374806 PMCID: PMC4220139 DOI: 10.5492/wjccm.v3.i4.102] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2014] [Revised: 09/24/2014] [Accepted: 10/27/2014] [Indexed: 02/06/2023] Open
Abstract
Invasive candidiasis (IC) bears a high risk of morbidity and mortality in the intensive care units (ICU). With the current advances in critical care and the use of wide-spectrum antibiotics, invasive fungal infections (IFIs) and IC in particular, have turned into a growing concern in the ICU. Further to blood cultures, some auxiliary laboratory tests and biomarkers are developed to enable an earlier detection of infection, however these test are neither consistently available nor validated in our setting. On the other hand, patients’ clinical status and local epidemiology data may justify the empiric antifungal approach using the proper antifungal option. The clinical approach to the management of IC in febrile, non-neutropenic critically ill patients has been defined in available international guidelines; nevertheless such recommendations need to be customized when applied to our local practice. Over the past three years, Iranian experts from intensive care and infectious diseases disciplines have tried to draw a consensus on the management of IFI with a particular focus on IC in the ICU. The established IFI-clinical forum (IFI-CF), comprising the scientific leaders in the field, has recently come up with and updated recommendation on the same (June 2014). The purpose of this review is to put together literature insights and Iranian experts’ opinion at the IFI-CF, to propose an updated practical overview on recommended approaches for the management of IC in the ICU.
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34
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Wang X, Fu YF, Wang RY, Li L, Cao YH, Chen YQ, Zhao HZ, Zhang QQ, Wu JQ, Weng XH, Cheng XJ, Zhu LP. Identification of clinically relevant fungi and prototheca species by rRNA gene sequencing and multilocus PCR coupled with electrospray ionization mass spectrometry. PLoS One 2014; 9:e98110. [PMID: 24835205 PMCID: PMC4024029 DOI: 10.1371/journal.pone.0098110] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2013] [Accepted: 04/28/2014] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Multilocus PCR coupled with electrospray ionization mass spectrometry (PCR/ESI-MS) is a new strategy for pathogen identification, but information about its application in fungal identification remains sparse. METHODS One-hundred and twelve strains and isolates of clinically important fungi and Prototheca species were subjected to both rRNA gene sequencing and PCR/ESI-MS. Three regions of the rRNA gene were used as targets for sequencing: the 5' end of the large subunit rRNA gene (D1/D2 region), and the internal transcribed spacers 1 and 2 (ITS1 and ITS2 regions). Microbial identification (Micro ID), acquired by combining results of phenotypic methods and rRNA gene sequencing, was used to evaluate the results of PCR/ESI-MS. RESULTS For identification of yeasts and filamentous fungi, combined sequencing of the three regions had the best performance (species-level identification rate of 93.8% and 81.8% respectively). The highest species-level identification rate was achieved by sequencing of D1/D2 for yeasts (92.2%) and ITS2 for filamentous fungi (75.8%). The two Prototheca species could be identified to species level by D1/D2 sequencing but not by ITS1 or ITS2. For the 102 strains and isolates within the coverage of PCR/ESI-MS identification, 87.3% (89/102) achieved species-level identification, 100% (89/89) of which were concordant to Micro ID on species/complex level. The species-level identification rates for yeasts and filamentous fungi were 93.9% (62/66) and 75% (27/36) respectively. CONCLUSIONS rRNA gene sequencing provides accurate identification information, with the best results obtained by a combination of ITS1, ITS2 and D1/D2 sequencing. Our preliminary data indicated that PCR/ESI-MS method also provides a rapid and accurate identification for many clinical relevant fungi.
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Affiliation(s)
- Xuan Wang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Yong-Feng Fu
- Department of Medical Microbiology and Parasitology, Shanghai Medical College of Fudan University, Shanghai, China
| | - Rui-Ying Wang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Li Li
- Mycology Lab, Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China
| | - Ya-Hui Cao
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Yan-Qiong Chen
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Hua-Zhen Zhao
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Qiang-Qiang Zhang
- Mycology Lab, Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China
| | - Ji-Qin Wu
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Xin-Hua Weng
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Xun-Jia Cheng
- Department of Medical Microbiology and Parasitology, Shanghai Medical College of Fudan University, Shanghai, China
| | - Li-Ping Zhu
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
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35
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Preuner S, Lion T. Towards molecular diagnostics of invasive fungal infections. Expert Rev Mol Diagn 2014; 9:397-9. [DOI: 10.1586/erm.09.27] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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36
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Rapid antifungal susceptibility testing by matrix-assisted laser desorption ionization-time of flight mass spectrometry analysis. J Clin Microbiol 2013; 51:2964-9. [PMID: 23824764 DOI: 10.1128/jcm.00903-13] [Citation(s) in RCA: 92] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
The widespread use of antifungal agents, which is likely to expand with their enhanced availability, has promoted the emergence of drug-resistant strains. Antifungal susceptibility testing (AFST) is now an essential procedure for guiding appropriate antifungal therapy. Recently, we developed a matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS)-based method that enables the detection of fungal isolates with reduced echinocandin susceptibility, relying on the proteome changes that are detectable after a 15-h exposure of fungal cells to serial drug concentrations. Here, we describe a simplified version of this approach that facilitates discrimination of the susceptible and resistant isolates of Candida albicans after a 3-h incubation in the presence of "breakpoint" level drug concentrations of the echinocandin caspofungin (CSF). Spectra at concentrations of 0 (null), 0.03 (intermediate), and 32 (maximal) μg/ml of CSF were used to create individual composite correlation index (CCI) matrices for 65 C. albicans isolates, including 13 fks1 mutants. Isolates are then classified as susceptible or resistant to CSF if the CCI values of spectra at 0.03 and 32 μg/ml are higher or lower, respectively, than the CCI values of spectra at 0.03 and 0 μg/ml. In this way, the drug resistance of C. albicans isolates to echinocandin antifungals can be quickly assessed. Furthermore, the isolate categorizations determined using MALDI-TOF MS-based AFST (ms-AFST) were consistent with the wild-type and mutant FKS1 genotypes and the AFST reference methodology. The ms-AFST approach may provide a rapid and reliable means of detecting emerging antifungal resistance and accelerating the initiation of appropriate antifungal treatment.
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37
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Preuner S, Lion T. Species-specific identification of a wide range of clinically relevant fungal pathogens by the Luminex(®) xMAP technology. Methods Mol Biol 2013; 968:119-39. [PMID: 23296890 DOI: 10.1007/978-1-62703-257-5_9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
Invasive fungal infections (IFI) are a common cause of life-threatening events in immunocompromised patients. Early detection and identification of the fungal pathogen is an important prerequisite for timely onset of the most appropriate treatment. Methods based on fungal culture are often too slow to be clinically useful. Other approaches to the identification of fungal species, including molecular techniques, are often restricted to a small number of the most commonly occurring pathogens and are therefore of limited use in the clinical setting. The development of assays for the detection and identification of a broad-range of clinically relevant fungal species is therefore an urgently needed step towards optimized diagnostics of IFI.The Luminex(®) xMAP technology offers a platform for the establishment of multiplex assays permitting high-throughput analysis of up to 100 different target molecules in a single test. Here we describe a Luminex(®)-based multiplex assay permitting rapid detection and identification of 10 fungal genera and 29 different species, including both commonly occurring and emerging fungal pathogens.
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Affiliation(s)
- S Preuner
- Children's Cancer Research Institute (CCRI), Labdia Labordiagnostik, Vienna, Austria
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38
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Jiang Z, Wang Y, Wang W, Wang S, Xu B, Fan G, Dong G, Liu Y, Yao J, Miao Z, Zhang W, Sheng C. Discovery of highly potent triazole antifungal derivatives by heterocycle-benzene bioisosteric replacement. Eur J Med Chem 2013; 64:16-22. [DOI: 10.1016/j.ejmech.2013.04.025] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2012] [Revised: 02/27/2013] [Accepted: 04/10/2013] [Indexed: 11/27/2022]
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39
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Ferreira AV, Prado CG, Carvalho RR, Dias KST, Dias ALT. Candida albicans and non-C. albicans Candida species: comparison of biofilm production and metabolic activity in biofilms, and putative virulence properties of isolates from hospital environments and infections. Mycopathologia 2013; 175:265-72. [PMID: 23532754 DOI: 10.1007/s11046-013-9638-z] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2012] [Accepted: 03/11/2013] [Indexed: 11/26/2022]
Abstract
Candida albicans and, more recently, non-C. albicans Candida spp. are considered the most frequent fungi in hospitals. This study analyzed Candida spp. isolates and compared the frequency of different species, that is, C. albicans and non-C. albicans Candida spp., and the origins of isolates, that is, from hospital environments or infections. Yeast virulence factors were evaluated based on biofilm production and metabolic activity. Hemolysin production and the antifungal susceptibility profiles of isolates were also evaluated. Candida spp. were highly prevalent in samples collected from hospital environments, which may provide a reservoir for continuous infections with these yeasts. There were no differences in the biofilm productivity levels and metabolic activities of the environmental and clinical isolates, although the metabolic activities of non-C. albicans Candida spp. biofilms were greater than those of the C. albicans biofilms (p < 0.05). Clinical samples had higher hemolysin production (p < 0.05) and lower susceptibility to fluconazole (p < 0.05). Non-C. albicans Candida spp. predominated in samples collected from hospital environments and infections (p < 0.05). These species had a lower susceptibility to fluconazole and amphotericin B, and their biofilms had higher metabolic activities than those produced by C. albicans, which may explain the increased incidence of fungal infections with these yeasts during recent years.
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Affiliation(s)
- A V Ferreira
- Microbiology and Immunology Department, Biomedical Sciences Institute, Federal University of Alfenas (UNIFAL-MG), Alfenas, MG, Brazil
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40
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Champer J, Diaz-Arevalo D, Champer M, Hong TB, Wong M, Shannahoff M, Ito JI, Clemons KV, Stevens DA, Kalkum M. Protein targets for broad-spectrum mycosis vaccines: quantitative proteomic analysis of Aspergillus and Coccidioides and comparisons with other fungal pathogens. Ann N Y Acad Sci 2013; 1273:44-51. [PMID: 23230836 DOI: 10.1111/j.1749-6632.2012.06761.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Aspergillus species are responsible for most cases of fatal mold infections in immunocompromised patients, particularly in those receiving hematopoietic stem cell transplants. Experimental vaccines in mouse models have demonstrated a promising avenue of approach for the prevention of aspergillosis, as well as infections caused by other fungal pathogens, such as Coccidioides, the etiological agent of valley fever (coccidioidomycosis). Here, we investigated the hyphal proteomes of Aspergillus fumigatus and Coccidioides posadasii via quantitative MS(E) mass spectrometry with the objective of developing a vaccine that cross-protects against these and other species of fungi. Several homologous proteins with highly conserved sequences were identified and quantified in A. fumigatus and C. posadasii. Many abundant proteins from the cell wall of A. fumigatus present themselves as possible cross-protective vaccine candidates, due to the high degree of sequence homology to other medically relevant fungal proteins and low homologies to human or murine proteins.
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Affiliation(s)
- Jackson Champer
- Department of Immunology Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope, Duarte, California, USA
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Samonis G, Galanakis E, Ntaoukakis M, Sarchianaki E, Spathopoulou T, Dimopoulou D, Kofteridis DP, Maraki S. Effects of carbapenems and their combination with amikacin on murine gut colonisation by Candida albicans. Mycoses 2012; 56:105-9. [PMID: 22680984 DOI: 10.1111/j.1439-0507.2012.02212.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Carbapenems are broad-spectrum antibiotics increasingly used for the treatment of severe infections. We evaluated the effects of four carbapenems given as monotherapies or in combination with amikacin on the level of gastrointestinal colonisation by Candida albicans in a previously established mouse model. Adult male Crl : CD1 (ICR) BR mice were fed chow containing C. albicans or regular chow. The mice fed with Candida chow had their gut colonised by the yeast. Both groups were subsequently given imipenem, meropenem, ertapenem, doripenem or their combination with amikacin or normal saline subcutaneously for 10 days. Stool cultures were performed immediately before, at the end and 1 week after discontinuation of treatment. Candida-colonised mice treated with the antibiotics had higher counts of the yeast in their stools than control C. albicans-colonised animals treated with saline. All four carbapenems and their combination with amikacin caused a significant increase in C. albicans concentration. Mice fed regular chow and treated with the study antibiotics or saline did not have any Candida in their stools. Dissemination of Candida was not detected in any animal. These data suggest that carbapenems and carbapenem plus amikacin induce substantial increases in the murine intestinal concentration of C. albicans.
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Affiliation(s)
- George Samonis
- Division of Medicine, University of Crete, Crete, Greece
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42
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Bryan RA, Guimaraes AJ, Hopcraft S, Jiang Z, Bonilla K, Morgenstern A, Bruchertseifer F, Del Poeta M, Torosantucci A, Cassone A, Nosanchuk JD, Casadevall A, Dadachova E. Toward developing a universal treatment for fungal disease using radioimmunotherapy targeting common fungal antigens. Mycopathologia 2012; 173:463-71. [PMID: 22048869 PMCID: PMC4397502 DOI: 10.1007/s11046-011-9476-9] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2011] [Accepted: 08/26/2011] [Indexed: 01/20/2023]
Abstract
BACKGROUND Previously, we demonstrated the ability of radiolabeled antibodies recognizing the cryptococcal polysaccharide capsule to kill Cryptococcus neoformans both in vitro and in infected mice. This approach, known as radioimmunotherapy (RIT), uses the exquisite ability of antibodies to bind antigens to deliver microbicidal radiation. To create RIT reagents which would be efficacious against all major medically important fungi, we have selected monoclonal antibodies (mAbs) to common surface fungal antigens such as heat shock protein 60 (HSP60), which is found on the surface of diverse fungi; beta (1,3)-glucan, which is a major constituent of fungal cell walls; ceramide which is found at the cell surface, and melanin, a polymer present in the fungal cell wall. METHODS MAbs 4E12, an IgG2a to fungal HSP60; 2G8, an IgG2b to beta-(1,3)-glucan; and 6D2, an IgM to melanin, were labeled with the alpha particle emitting radionuclide 213-Bismuth ((213)Bi) using the chelator CHXA". B11, an IgM antibody to glucosylceramide, was labeled with the beta emitter 188-Rhenium ((188)Re). Model organisms Cryptococcus neoformans and Candida albicans were used to assess the cytotoxicity of these compounds after exposure to either radiolabeled mAbs or controls. RESULTS (213)Bi-mAbs to HSP60 and to the beta-(1,3)-glucan each reduced the viability of both fungi by 80-100%. The (213)Bi-6D2 mAb to melanin killed 22% of C. neoformans, but did not kill C. albicans. B11 mAb against fungal ceramide was effective against wild-type C. neoformans, but was unable to kill a mutant lacking the ceramide target. Unlabeled mAbs and radiolabeled irrelevant control mAbs caused no killing. CONCLUSION Our results suggest that it is feasible to develop RIT against fungal pathogens by targeting common antigens and such an approach could be developed against fungal diseases for which existing therapy is unsatisfactory.
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Affiliation(s)
- R. A. Bryan
- Albert Einstein College of Medicine, 1695A Eastchester Rd., Bronx, NY 10461, USA
| | - A. J. Guimaraes
- Albert Einstein College of Medicine, 1695A Eastchester Rd., Bronx, NY 10461, USA
| | - S. Hopcraft
- Albert Einstein College of Medicine, 1695A Eastchester Rd., Bronx, NY 10461, USA
| | - Z. Jiang
- Albert Einstein College of Medicine, 1695A Eastchester Rd., Bronx, NY 10461, USA
| | - K. Bonilla
- Albert Einstein College of Medicine, 1695A Eastchester Rd., Bronx, NY 10461, USA
| | | | | | - M. Del Poeta
- Medical University of South Carolina, Charleston, SC, USA
| | | | - A. Cassone
- Istituto Superiore di Sanita, Rome, Italy
| | - J. D. Nosanchuk
- Albert Einstein College of Medicine, 1695A Eastchester Rd., Bronx, NY 10461, USA
| | - A. Casadevall
- Albert Einstein College of Medicine, 1695A Eastchester Rd., Bronx, NY 10461, USA
| | - E. Dadachova
- Albert Einstein College of Medicine, 1695A Eastchester Rd., Bronx, NY 10461, USA
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Beinborn NA, Du J, Wiederhold NP, Smyth HDC, Williams RO. Dry powder insufflation of crystalline and amorphous voriconazole formulations produced by thin film freezing to mice. Eur J Pharm Biopharm 2012; 81:600-8. [PMID: 22569473 DOI: 10.1016/j.ejpb.2012.04.019] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2011] [Revised: 04/21/2012] [Accepted: 04/24/2012] [Indexed: 12/31/2022]
Abstract
Attention has begun to focus on the pulmonary delivery of antifungal agents for invasive fungal infections as inhalation of the fungal spores is often the initial step in the pathogenesis of many of these infections, including invasive pulmonary aspergillosis (IPA). IPA in immunocompromised patients has high mortality rates despite current systemic (oral or intravenous) therapies. In this study, particulate voriconazole (VRC) formulations were designed with suitable properties for inhalation using thin film freezing (TFF), a particle engineering process capable of producing low-density porous aggregate particles. Nanostructured amorphous morphology of VRC was less favorable in vitro and in vivo than microstructured crystalline morphology, despite being a poorly water-soluble compound. Using a Handihaler dry powder inhaler (DPI), microstructured crystalline TFF-VRC and nanostructured amorphous TFF-VRC-PVP K25 (1:3) had fine particle fractions of 37.8% and 32.4% and mass median aerodynamic diameters of 4.2 and 5.2 μm, respectively. Single dose 24-h pharmacokinetic studies were conducted in ICR mice. AUC(0-24h) in the lung tissue and plasma was 452.6 μg h/g wet lung weight and 38.4 μg h/mL, respectively, following a 10mg/kg insufflated dose of TFF-VRC directly into the lungs of the mice, while AUC(0-24 h) in the lung tissue and plasma was 232.1 μg h/g wet lung weight and 18.6 μg h/mL, respectively, following a 10mg/kg insufflated dose of TFF-VRC-PVP K25 (1:3). High concentrations of VRC in lung tissue coupled with clinically relevant plasma concentrations suggest that pulmonary delivery of microstructured crystalline VRC could potentially be a beneficial strategy for administration of VRC to patients with invasive pulmonary fungal infections.
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Affiliation(s)
- Nicole A Beinborn
- College of Pharmacy, The University of Texas at Austin, TX 78712, USA.
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44
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Dai T, Fuchs BB, Coleman JJ, Prates RA, Astrakas C, St Denis TG, Ribeiro MS, Mylonakis E, Hamblin MR, Tegos GP. Concepts and principles of photodynamic therapy as an alternative antifungal discovery platform. Front Microbiol 2012; 3:120. [PMID: 22514547 PMCID: PMC3322354 DOI: 10.3389/fmicb.2012.00120] [Citation(s) in RCA: 158] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2012] [Accepted: 03/13/2012] [Indexed: 01/25/2023] Open
Abstract
Opportunistic fungal pathogens may cause superficial or serious invasive infections, especially in immunocompromised and debilitated patients. Invasive mycoses represent an exponentially growing threat for human health due to a combination of slow diagnosis and the existence of relatively few classes of available and effective antifungal drugs. Therefore systemic fungal infections result in high attributable mortality. There is an urgent need to pursue and deploy novel and effective alternative antifungal countermeasures. Photodynamic therapy (PDT) was established as a successful modality for malignancies and age-related macular degeneration but photodynamic inactivation has only recently been intensively investigated as an alternative antimicrobial discovery and development platform. The concept of photodynamic inactivation requires microbial exposure to either exogenous or endogenous photosensitizer molecules, followed by visible light energy, typically wavelengths in the red/near infrared region that cause the excitation of the photosensitizers resulting in the production of singlet oxygen and other reactive oxygen species that react with intracellular components, and consequently produce cell inactivation and death. Antifungal PDT is an area of increasing interest, as research is advancing (i) to identify the photochemical and photophysical mechanisms involved in photoinactivation; (ii) to develop potent and clinically compatible photosensitizers; (iii) to understand how photoinactivation is affected by key microbial phenotypic elements multidrug resistance and efflux, virulence and pathogenesis determinants, and formation of biofilms; (iv) to explore novel photosensitizer delivery platforms; and (v) to identify photoinactivation applications beyond the clinical setting such as environmental disinfectants.
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Affiliation(s)
- Tianhong Dai
- Wellman Center for Photomedicine, Massachusetts General Hospital Boston, MA, USA
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45
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Total synthesis and structure–activity relationships of caspofungin-like macrocyclic antifungal lipopeptides. Tetrahedron 2012. [DOI: 10.1016/j.tet.2012.02.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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46
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Jandric Z, Schüller C. Stress response in Candida glabrata: pieces of a fragmented picture. Future Microbiol 2012; 6:1475-84. [PMID: 22122443 DOI: 10.2217/fmb.11.131] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Candida glabrata is closely related to yeast but obviously adapted to human commensalism. Communication with the environment is important to adjust allocation of resources between protection and proliferation in order to adapt to different situations in and outside of the host. Gene transcription regulated by environmental conditions is a major response strategy of simple fungal organisms. Differences to yeast include an extended repertoire of adhesive genes, and high drug, starvation and stress resistance. These properties largely do not originate from novel virulence genes but rather from adaptations of the transcriptional wiring. C. glabrata signaling pathways providing stress protection are adopted to meet conditions possibly encountered in a host-pathogen confrontation. The view on C. glabrata is getting clearer and points to a simple strategy combining resilience and a few adaptations.
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Affiliation(s)
- Zeljkica Jandric
- DAGZ, Department for Applied Genetics & Cell Biology, University of Natural Resources & Life Sciences, Vienna, BOKU, UFT-Campus Tulln, 24 3430 Tulln, Austria
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47
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Yao J, Liu H, Zhou T, Chen H, Miao Z, Sheng C, Zhang W. Total synthesis and structure-activity relationships of new echinocandin-like antifungal cyclolipohexapeptides. Eur J Med Chem 2012; 50:196-208. [PMID: 22348827 DOI: 10.1016/j.ejmech.2012.01.054] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2011] [Revised: 01/27/2012] [Accepted: 01/27/2012] [Indexed: 11/30/2022]
Abstract
A series of new echinocandin-like cyclolipohexapeptides were designed and total synthesized via solution phase [3 + 3]-segment coupling strategy with an attempt to improve antifungal activity. The designed compounds showed potent antifungal activities with broad spectrum. In particular, 11 compounds (i.e. 28a-e, 28g, 28i-j, 29a, 29c and 29e) showed better in vitro antifungal activities against Candida albicans or Aspergillus fumigatus than caspofungin. Moreover, the synthesized compounds provided new SAR information for the echinocandins. The findings in this work suggested that the "left" tripeptide segment of cyclolipohexapeptide scaffold might be a hydrophilic structural motif, whereas the "right" lipopeptide segment was preferred as a hydrophobic core. The amino acid component of the cyclolipohexapeptide scaffold could significantly affect the SAR of the side chains.
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Affiliation(s)
- Jianzhong Yao
- Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
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48
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Nosanchuk JD, Dadachova E. Radioimmunotherapy of fungal diseases: the therapeutic potential of cytocidal radiation delivered by antibody targeting fungal cell surface antigens. Front Microbiol 2012; 2:283. [PMID: 22275913 PMCID: PMC3257868 DOI: 10.3389/fmicb.2011.00283] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2011] [Accepted: 12/28/2011] [Indexed: 01/26/2023] Open
Abstract
Radioimmunotherapy is the targeted delivery of cytocidal radiation to cells via specific antibody. Although mature for the treatment of cancer, RIT of infectious diseases is in pre-clinical development. However, as there is an obvious and urgent need for novel approaches to treat infectious diseases, RIT can provide us with a powerful approach to combat serious diseases, including invasive fungal infections. For example, RIT has proven more effective than standard amphotericin B for the treatment of experimental cryptococcosis. This review will discuss the concepts of RIT, its applications for infectious diseases, and the strides made to date to bring RIT of infectious diseases to fruition. Finally, we will discuss the potential of PAN-FUNGAL RIT, the targeting of conserved fungal cell surface antigens by RIT, as a treatment modality for fungi prior to the formal microbiological identification of the specific pathogen. In sum, RIT provides a mechanism for the targeted killing of drug susceptible or resistant fungi irrespective of the host immune status and may dramatically reduce the length of therapy currently required for many invasive fungal diseases.
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Affiliation(s)
- Joshua D Nosanchuk
- Department of Medicine, Albert Einstein College of Medicine Bronx, NY, USA
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49
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Kume H, Yamazaki T, Togano T, Abe M, Tanuma H, Kawana S, Okudaira M. Epidemiology of visceral mycoses in autopsy cases in Japan: comparison of the data from 1989, 1993, 1997, 2001, 2005 and 2007 in Annual of Pathological Autopsy Cases in Japan. Med Mycol J 2012; 52:117-27. [PMID: 21788723 DOI: 10.3314/jjmm.52.117] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
The data on visceral mycoses reported in the " Annual of Pathological Autopsy Cases in Japan " were analyzed epidemiologically every four years from 1989 to 2005, and in 2007. The frequency rates of visceral mycoses dropped sharply between 1989 (4.5%) and 1994 (3.2%), but by 2001 had risen again and have remained (4.4-4.6%) generally stable since then. The predominant causative agents were Candida and Aspergillus. Although the rate of candidosis showed a gradual decrease, the rate of aspergillosis showed an increase by degrees. Furthermore, the rate of aspergillosis exceeded that of candidosis in 1994, and the difference in the rates between the two conditions apparently further increased until 2001. After 2005, however no changes in this difference were observed. For complicated infections, the incidence of coinfection with Aspergillus and Candida showed a decreasing, and that with Aspergillus and Zygomycetes showed an increasing tendency. Severe infections with Zygomycetes showed a clear increase from 57.4% in 1989 to 88.9% in 2007. Comparing underlying diseases with mycoses in 1989 and 2007, leukemia (including myelodysplastic syndrome) decreased from 26.1% to 18.8% and bacterial infections (including interstitial pneumonia) increased from 11.1% to 22.1%. By age, the highest frequency rate of mycoses was observed in the range of 60-79 years, and the frequency rate of exogenous fungal infections such as aspergillosis, cryptococcosis, zygomycosis and trichosporonosis showed an increasing trend in the less than one-year old group.
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Affiliation(s)
- Hikaru Kume
- Department of Pathology, School of Medicine, Kitasato University, Japan
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50
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Bin-Hussain I. Fungal Infections. TEXTBOOK OF CLINICAL PEDIATRICS 2012:1061-1069. [DOI: 10.1007/978-3-642-02202-9_96] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
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