Expression Patterns of ABC Transporter Genes in Fl

Authors: Atefeh Abdollahi Gohar Hamid Badali Tahereh Shokohi Mojtaba Nabili Nasrin Amirrajab Maryam Moazeni

Publish Date: 2016/10/15

Volume: 182, Issue: 3-4, Pages: 273-284

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Abstract

Clinical management of fungal diseases is compromised by the emergence of antifungal drug resistance in fungi which leads to elimination of available drug classes as treatment options An understanding of antifungal resistance at molecular level is therefore essential for the development of strategies to combat the resistance This study presents the assessment of molecular mechanisms associated with fluconazole resistance in clinical Candida glabrata isolates originated from Iran Taking seven distinct fluconazoleresistant C glabrata isolates realtime PCRs were performed to evaluate the alternations in the regulation of the genes involved in drug efflux including CgCDR1 CgCDR2 CgSNQ2 and CgERG11 Gainoffunction GOF mutations in CgPDR1 alleles were determined by DNA sequencing Crossresistance to fluconazole itraconazole and voriconazole was observed in 25  of the isolates In the present study six amino acid substitutions were identified in CgPdr1 among which W297R T588A and F575L were previously reported whereas D243N H576Y and P915R are novel CgCDR1 overexpression was observed in 571  of resistant isolates However CgCDR2 was not coexpressed with CgCDR1 CgSNQ2 was upregulated in 714  of the cases CgERG11 overexpression does not seem to be associated with azole resistance except for isolates that exhibited azole crossresistance The pattern of efflux pump gene upregulation was associated with GOF mutations observed in CgPDR1 These results showed that drug efflux mediated by adenosine5triphosphate ATPbinding cassette transporters especially CgSNQ2 and CgCDR1 is the predominant mechanism of fluconazole resistance in Iranian isolates of C glabrata Since some novel GOF mutations were found here this study also calls for research aimed at investigating other new GOF mutations to reveal the comprehensive understanding about effluxmediated resistance to azole antifungal agents

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