title: Genetic Diversity andIn VitroAntifungal Susceptibility of 200 Clinical and Environmental Aspergillus flavus Isolates.
abstract: Aspergillus flavushas been frequently reported as the leading cause of invasive aspergillosis in certain tropical and subtropical countries. Two hundredA. flavusstrains originating from clinical and environmental sources and collected between 2008 and 2015 were phylogenetically identified at the species level by analyzing partial β-tubulin and calmodulin genes.In vitroantifungal susceptibility testing was performed against antifungals using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution method. In addition, genotyping was performed using a short-tandem-repeat (STR) assay of a panel of six microsatellite markers (A. flavus2A, 2B, 2C, 3A, 3B, and 3C), in order to determine the genetic variation and the potential relationship between clinical and environmental isolates. The geometric means of the minimum inhibitory concentrations/minimum effective concentrations (MICs/MECs) of the antifungals across all isolates were (in increasing order): posaconazole, 0.13 mg/liter; anidulafungin, 0.16 mg/liter; itraconazole, 0.29 mg/liter; caspofungin, 0.42 mg/liter; voriconazole, 0.64 mg/liter; isavuconazole, 1.10 mg/liter; amphotericin B, 3.35 mg/liter; and flucytosine, 62.97 mg/liter. All of the clinical isolates were genetically different. However, an identical microsatellite genotype was found between a clinical isolate and two environmental strains. In conclusion, posaconazole and anidulafungin showed the greatestin vitroactivity among systemic azoles and echinocandins, respectively. However, the majority of theA. flavusisolates showed reduced susceptibility to amphotericin B. Antifungal susceptibility ofA. flavuswas not linked with the clinical or environmental source of isolation. Microsatellite genotyping may suggest an association between clinical and environmental strains, although this requires further investigation.
authors.affiliation: Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran.|Department of Medical Mycology and Parasitology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.|Department of Medical Mycology and Parasitology, School of Medicine, Babol University of Medical Sciences, Babol, Iran.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Taghizadeh-Armaki
authors.affiliation: Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran.|Department of Medical Mycology and Parasitology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Mohammad Taghi
authors.identifier: 0000-0001-6415-4648
authors.initials: MT
authors.lastname: Hedayati
authors.affiliation: Department of Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Saham
authors.initials: S
authors.lastname: Ansari
authors.affiliation: Department of Medical Mycology and Parasitology, School of Medicine, Babol University of Medical Sciences, Babol, Iran.
authors.forename: Saeed Mahdavi
authors.initials: SM
authors.lastname: Omran
authors.affiliation: School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Sasan
authors.initials: S
authors.lastname: Saber
authors.affiliation: Department of Biochemistry, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Haleh
authors.initials: H
authors.lastname: Rafati
authors.affiliation: Department of Medical Microbiology, Radboudumc, Nijmegen, the Netherlands.|Center of Expertise in Mycology Radboudumc/CWZ, Nijmegen, the Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Zoll
authors.affiliation: Department of Medical Microbiology, Radboudumc, Nijmegen, the Netherlands.|Center of Expertise in Mycology Radboudumc/CWZ, Nijmegen, the Netherlands.
authors.forename: Henrich A
authors.initials: HA
authors.lastname: van der Lee
authors.affiliation: Department of Medical Microbiology, Radboudumc, Nijmegen, the Netherlands.|Center of Expertise in Mycology Radboudumc/CWZ, Nijmegen, the Netherlands.
authors.forename: Willem J G
authors.initials: WJG
authors.lastname: Melchers
authors.affiliation: Department of Medical Microbiology, Radboudumc, Nijmegen, the Netherlands.|Center of Expertise in Mycology Radboudumc/CWZ, Nijmegen, the Netherlands.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Verweij
authors.affiliation: Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran Seyedmousavi@nih.gov.|Department of Medical Microbiology, Radboudumc, Nijmegen, the Netherlands.|Center of Expertise in Mycology Radboudumc/CWZ, Nijmegen, the Netherlands.
authors.forename: Seyedmojtaba
authors.identifier: 0000-0002-6194-7447
authors.initials: S
authors.lastname: Seyedmousavi
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000382:microbiology; D001231:Aspergillus flavus / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D002147:Calmodulin / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests; D018895:Microsatellite Repeats / Q000235:genetics*; D014404:Tubulin / Q000235:genetics
chemical_list: D000935:Antifungal Agents; D002147:Calmodulin; D014404:Tubulin
keywords: Aspergillus flavus; Iran; antifungal susceptibility; clinical; environmental; genotyping; molecular epidemiology