Tehran University of Medical Sciences Acta Medica Iranica 0044-6025 54 7 2016 07 09 458 464 EN Shirin Farahyar Department of Medical Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Farideh Zaini Department of Medical Mycology and Parasitology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Parivash Kordbacheh Department of Medical Mycology and Parasitology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Sassan Rezaie Department of Medical Mycology and Parasitology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Mehraban Falahati Department of Medical Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Mahin Safara Department of Medical Mycology and Parasitology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Reza Raoofian Legal Medicine Organization Research Center, Genetic Laboratory, Legal Medicine Organization, Mashhad, Iran. Kamran Hatami Department of Language, School of Management and Information Sciences, Iran University of Medical Sciences, Tehran, Iran. Masoumeh Mohebbi Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran. Mansour Heidari Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. AND Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. AND Department of Molecular Biology and Genetics, Islamic Azad University, Boushehr Branch, Boushehr, Iran. 2015 10 14 2016 03 05 Acquired azole resistance in opportunistic fungi causes severe clinical problems in immunosuppressed individuals. This study investigated the molecular mechanisms of azole resistance in clinical isolates of Candida glabrata. Six unmatched strains were obtained from an epidemiological survey of candidiasis in immunocompromised hosts that included azole and amphotericin B susceptible and azole resistant clinical isolates. Candida glabrata CBS 138 was used as reference strain. Antifungal susceptibility testing of clinical isolates was evaluated using Clinical and Laboratory Standards Institute (CLSI) methods. Complementary DNA-amplified fragment length polymorphism (cDNA-AFLP) technology, semi-quantitative RT-PCR, and sequencing were employed for identification of potential genes involved in azole resistance. Candida glabrata Candida drug resistance 1 (CgCDR1) and Candida glabrata Candida drug resistance 2 (CgCDR2) genes, which encode for multidrug transporters, were found to be upregulated in azole-resistant isolates (≥2-fold). Fatty acid activator 1 (FAA1) gene, belonging to Acyl-CoA synthetases, showed expression in resistant isolates ≥2-fold that of the susceptible isolates and the reference strain. This study revealed overexpression of the CgCDR1, CgCDR2, and FAA1 genes affecting biological pathways, small hydrophobic compounds transport, and lipid metabolism in the resistant clinical C.glabrata isolates. https://acta.tums.ac.ir/index.php/acta/article/view/4972 https://acta.tums.ac.ir/index.php/acta/article/download/4972/4815