title: Expression of Efflux Pumps and Fatty Acid Activator One Genes in Azole Resistant Candida Glabrata Isolated From Immunocompromised Patients.
abstract: 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.
authors.affiliation: Department of Medical Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Shirin
authors.initials: S
authors.lastname: Farahyar
authors.affiliation: Department of Medical Mycology and Parasitology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Farideh
authors.initials: F
authors.lastname: Zaini
authors.affiliation: Department of Medical Mycology and Parasitology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Parivash
authors.initials: P
authors.lastname: Kordbacheh
authors.affiliation: Department of Medical Mycology and Parasitology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Sassan
authors.initials: S
authors.lastname: Rezaie
authors.affiliation: Department of Medical Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mehraban
authors.initials: M
authors.lastname: Falahati
authors.affiliation: Department of Medical Mycology and Parasitology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mahin
authors.initials: M
authors.lastname: Safara
authors.affiliation: Legal Medicine Organization Research Center, Genetic Laboratory, Legal Medicine Organization, Mashhad, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Raoofian
authors.affiliation: Department of Language, School of Management and Information Sciences, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Kamran
authors.initials: K
authors.lastname: Hatami
authors.affiliation: Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Mohebbi
authors.affiliation: 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.
authors.forename: Mansour
authors.initials: M
authors.lastname: Heidari
mesh_terms: D000328:Adult; D054458:Amplified Fragment Length Polymorphism Analysis; D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000276:immunology / Q000494:pharmacology*; D041221:Candida glabrata / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D002177:Candidiasis / Q000382:microbiology; D003066:Coenzyme A Ligases / Q000378:metabolism*; D025141:Drug Resistance, Fungal / Q000235:genetics; D005260:Female; D019450:Genes, MDR; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D008875:Middle Aged
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D003066:Coenzyme A Ligases; C511244:Faa1 protein, S cerevisiae
keywords: Candida azole resistance; Candida glabrata; CgCDR1; CgCDR2; Fatty acid activator one; cDNA-AFLP method