P113 Expression profile of ABC and MFS multi-drug transporter genes in terbinafine- and fluconazole-resistant Trichophyton spp.

Abstract

Objectives: Over the past few decades, an unprecedented increase in recalcitrant and chronic dermatophytosis with atyp-ical clinical presentations have been noted in the Indian subcontinent. Recent studies have reported Trichophyton mentagro-phytes/interdigitale complex as predominant etiological agent of chronic/recurrent dermatophytosis followed by T. rubrum. Multiple factors, including unregulated use of antifungal drugs, poor compliance to treatment, and irrational fixed-drug com-binations are associated with emerging resistance. However, molecular studies investigating the underlying mechanisms related to terbinafine and fluconazole resistance in dermatophytes are sparse. The present study was designed to explore the role of multidrug efflux transporters in terbinafine-and fluconazole-resistant T. mentagrophytes/interdigitale complex and T. rubrum. Method(s): The expression of MDR transporter genes was evaluated in 36 isolates with terbinafine resistance (with or without F397L or L393F mutation in squalene epoxidase gene, SE) of T. mentagrophytes/interdigitale complex (n = 26), and T. rubrum (n = 10) isolates along with 16 susceptible wild-type isolates of T. mentagrophytes/interdigitale complex (n = 10), and T. rubrum (n = 6) isolates. In addition, 19 fluconazole-resistant T. mentagrophytes/interdigitale complex (n = 11), and T. rubrum (n = 8) isolates along with 13 susceptible T.mentagrophytes/interdigitale complex (n = 9), and T.rubrum (n = 4) were also included.Quantitative real-time PCR (qRT-PCR) was used to evaluate the expression of ABC transporter (MDR1, MDR2, MDR3, MDR4, and MDR5) and MFS transporter genes (MFS1 and MFS2). Result(s): In terbinafine-resistant T. mentagrophytes/interdigitale complex, the mean expression of MDR1 and MDR2 was 4.98 and 5.27-fold in isolates with wild-type SE, compared with 0.64 and 1.04-fold in isolates with non-wildtype SE gene (P