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Voriconazole Resistance Genes in Aspergillus Flavus Clinical Isolates Publisher Pubmed



Zaini F1 ; Lotfali E2 ; Fattahi A3 ; Siddig E4 ; Farahyar S5, 6 ; Kouhsari E7 ; Saffari M8
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Authors Affiliations
  1. 1. Department of Medical Parasitology and Mycology, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Medical Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  3. 3. Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Mycetoma Research Center, University of Khartoum, Khartoum, Sudan
  5. 5. Microbial Biotechnology Research Center(MBIRC), School of Medicine, Iran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Medical Mycology, Faculty of Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
  7. 7. Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
  8. 8. Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran

Source: Journal de Mycologie Medicale Published:2020


Abstract

Objective: The present study was designed to discover novel biomarkers involved in voriconazole resistance in clinical isolates of Aspergillus flavus. Materials and methods: Two voriconazole non-wild-type and two voriconazole-wild-type A. flavus clinical isolates were selected to evaluate possible molecular mechanism involved in A. flavus resistance to voriconazole using the mutation assessment, Quantitative real- time PCR of cyp51A and cyp51C genes and complementary DNA- amplified fragment length polymorphism technique. Results: No mutations were seen in the cyp51A and cyp51C genes in voriconazole non-wild-type isolates compared to wild- type and reference strains. Regarding to mRNA expression results, no changes were observed in expression fold of cyp51A and cyp51C mRNA expression level in first non- wild- type isolate compared to wild-type isolate. For second isolate cyp51C mRNA expression level was down regulated (5.6 fold). The set of genes including ABC fatty acid transporter XM- 002375835 and aldehydereductase XM- 002376518 and three unknown functional genes were identified. Based on results, the over-expression of AKR1 and ABC fatty acid transporter in the voriconazole non- wild- type isolates suggests these genes could represent a novel molecular marker linked to the voriconazole resistance in A. flavus. Conclusion: The results obtained in this study showed a novel finding as the authors identified AKR1 and ABC fatty acid transporter genes as possible voriconazole target genes in Iranian clinical isolates of A. flavus. © 2020
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