Integrated Genomic and Phenotypic Analyses Reveal Convergent Resistance Patterns in Clinical Candida tropicalis Isolates

Abstract

BACKGROUND: The incidence of Candida tropicalis isolation is increasing in hospital settings. High azole resistance and mortality rates make it a pathogen that requires further analysis. METHODS: Fourteen azole resistant Candida glabrata clinical isolates were collected from a Lebanese hospital and analysed through whole genome sequencing for single nucleotide polymorphisms in key resistance and virulence genes, and for phylogenetic relatedness. Isolates were then characterised for pathogenicity related attributes. RESULTS: All isolates had Lys314Glu mutation in ERG20 with multiple isolates displaying numerous shared mutations, such as Glu291Lys in CDR2 and Ala16Thr in CDR3. With the exception of two isolates that clustered together, most isolates were over 99.6% identical based on a genomic heatmap, implying high relatedness consistent with localised clonal expansion, although SNP differences appeared too high to support this. However, the isolates exhibited increased ergosterol and chitin content, as well as upregulation of drug efflux pumps resulting in drug resistance. CONCLUSION: Our hospital isolates showed convergent resistant pathways, with many isolates having both shared and unique mutations and a high degree of genomic similarities.