Pan-azole-resistant Candida tropicalis carrying homozygous erg11 mutations at position K143R: A new emerging superbug?

Abstract

Objectives: Candidaemia is a public health problem mainly in hospitalized individuals worldwide. In Brazil, Candida albicans is the most prevalent species that causes candidaemia, followed by Candida tropicalis and Candida parapsilosis. Few data on the abundance of antifungal resistance are available for Latin America. Methods: We analysed the frequency of azole and echinocandin resistance in Candida isolates (n=75) collected between 2012 and 2014 at the University Hospital of Federal University of Juiz de Fora (Brazil). The primary targets erg11 (azoles) and fks1 (echinocandins) were sequenced and modelled at the protein level. Antifungal susceptibility testing was performed according to CLSI (M27-A3 and M27-S4) and according to EUCAST. Results: The three most frequent species were C. albicans (38.0%), C. tropicalis (30.0%) and Candida glabrata (17.0%). Azole resistance was observed in 27.0% of all Candida isolates, while 20.0% of all isolates were echinocandin resistant. A novel mutation in erg11 at location K143R was found to be associated with phenotypically pan-azole-resistant C. tropicalis isolates. This mutation maps near the active binding site of erg11 and is likely to confer pan-azole resistance to C. tropicalis. Conclusions: A novel point mutation (K143R) located in the erg11 gene of C. tropicalis was found in pan-azoleresistant strains. According to our protein homology model, it is very likely that the mutation K143R causes panazole resistance in C. tropicalis. Moreover, an up-regulation of ABC transporters was observed, which can add up to a pan-azole-resistant phenotype.