Author/Authors :
Fattahi، Azam نويسنده Department of Medical Mycology and Parasitology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran , , Zaini، Farideh نويسنده Department of Parasitology and Mycology, School of Public Health, Institute of Public Health Researches, Tehran University of Medical Sciences, Tehran, IR Iran , , Kordbacheh، Parivash نويسنده , , Rezaie، Sasan نويسنده Department of Medical Mycology and Parasitology, School of Public Health and Institute of Public Health Research,Tehran, IR Iran , , Safara، Mahin نويسنده Department of Parasitology and Mycology, School of Public Health, Institute of Public Health Researches, Tehran University of Medical Sciences, Tehran, IR Iran , , Fateh، Roohollah نويسنده Department of Microbiology and Immunology, Faculty of Medicine, Qom University of Medical Sciences, Qom, IR Iran , , Farahyar، Shirin نويسنده Department of Medical Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Farahyar, Shirin , Seyed Kanani، Ali reza نويسنده , , Heidari، Mansour نويسنده Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Heidari, Mansour
Abstract :
Voriconazole Resistance (VRC-R) in Aspergillus flavus isolates impacts the management of aspergillosis, since azoles are the first choice for prophylaxis and therapy. However, to the best of our knowledge, the mechanisms underlying voriconazole resistance are poorly understood. The present study was designed to evaluate mRNA expression levels of cyp51A and mdr1 genes in voriconazole resistant A. flavus by a Real-Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) technique. Five A. flavus isolates with resistance to VRC were examined by a RT-PCR approach. Four out of five isolates revealed cyp51A and mdr1 mRNA overexpression. Interestingly, the isolate, which was negative for cyp51A and mdr1 mRNA expression showed a high voriconazole Minimum Inhibitory Concentration (MIC). Furthermore, a computational-based analysis predicted that voriconazole resistance could be mediated through cooperation with a network protein interaction. Our experimental and in silico findings may provide new insight in the complex molecular pathways of drug resistance and also could assist design an efficient therapeutic strategy for aspergillosis treatment
