Overexpression of efflux pump transporter genes and mutations in ERG11 pave the way to fluconazole resistance in Candida tropicalis: A study from a North India region

Abstract

Introduction: Fluconazole resistance in Candida tropicalis health care-associated infections is increasing. We investigated the role of efflux pump and mutations in ERG11p conferring fluconazole resistance in C. tropicalis.

Materials and methods: A total of 17 C. tropicalis clinical isolates, including fluconazole-resistant and fluconazole-susceptible/fluconazole-susceptible dose-dependent isolates, were collected from a tertiary care centre in a North India region between 2015 and 2018. Antifungal susceptibility, reversal of fluconazole resistance by tacrolimus, ERG11 amplification and its sequencing and a quantitative polymerase chain reaction (PCR) assay for expression analysis of ERG11, MDR1 and CDR1 genes were performed.

Results and discussion: Synergism between fluconazole and tacrolimus was observed in all resistant C. tropicalis isolates. Overexpression of all the three genes, MDR1, ERG11 and CDR1, was observed in resistant isolates (P = 0.05). Among resistant isolates, mutations leading to amino acid substitution were seen in two, Ct10 (glysine464serine) and Ct16 (tyrosine132phenylalanine; serine154phenylalanine).

Conclusion: Overexpression in efflux pump transporter genes, together with mutations in ERG11, lead to fluconazole resistance among C. tropicalis. To the best of our knowledge, this is the first study on the C. tropicalis fluconazole resistance mechanism from the North India region.

Keywords: C. tropicalis; ERG11 mutation; Fluconazole-resistant; MDR1 overexpression; Resistance reversal.