Azole and echinocandin resistance mechanisms and genotyping of Candida tropicalis in Japan: cross-boundary dissemination and animal-human transmission of C. tropicalis infection

Abstract

Objectives: To assess the prevalence and genetic basis of antifungal resistance mechanisms as well as the genotyping of Candida tropicalis from clinical and non-clinical sources in Japan.

Methods: Eighty C. tropicalis isolates, including 32 clinical isolates recovered from 29 patients and 48 non-clinical isolates recovered from 24 different sources (animals and the environment) were evaluated. All isolates were tested phenotypically for resistance to a wide range of antifungals and genotypically for resistance mechanisms to azole and echinocandin. Furthermore, all the isolates were genotyped by multilocus sequence typing (MLST).

Results: Phenotypically, 30.2% (16/53) of the isolates were azole-resistant, with high levels of azole resistance among clinical isolates (51.7%; 15/29) and low levels (4.2%; 1/24) among non-clinical isolates. None of the isolates were reported as echinocandin resistant, with 60.4% (32/53) of the isolates intermediate to caspofungin. Azole resistance was basically attributed to high expression levels of drug efflux transporter genes (CDR2 and CDR3), transcription factors (TAC1 and UPC2) and ergosterol biosynthesis pathway HMG gene. No FKS1 hot spot 1 (HS1) or HS2 missense mutations were detected in any of the isolates. MLST analysis revealed 36 different sequence types (STs), with the first identification of 23 new STs. Phylogenetic analysis confirmed the close relationship between the clinical and non-clinical isolates, with identifications of ST232 and ST933 among patients and marine mammals.

Conclusion: Our results confirmed the emergence of azole resistance in C. tropicalis in Japan. Furthermore, phylogenetic analysis confirmed the transboundary dissemination and cross-transmission of C. tropicalis between humans and animals.

Keywords: Animal–human transmission; Azole resistance; Candida tropicalis; Dissemination of Candida tropicalis; Echinocandin resistance; Multilocus sequence type genotyping.