Whole Genome Sequencing Shows Genetic Diversity, as Well as Clonal Complex and Gene Polymorphisms Associated with Fluconazole Non-Susceptible Isolates of <i>Candida tropicalis</i>

oleh: Caitlin Keighley, Mailie Gall, Sebastiaan J. van Hal, Catriona L. Halliday, Louis Yi Ann Chai, Kean Lee Chew, Chayanika Biswas, Monica A. Slavin, Wieland Meyer, Vitali Sintchenko, Sharon C. A. Chen

Format: Article
Diterbitkan: MDPI AG 2022-08-01

Deskripsi

Resistance to azoles in <i>Candida tropicalis</i> is increasing and may be mediated by genetic characteristics. Using whole genome sequencing (WGS), we examined the genetic diversity of 82 bloodstream <i>C. tropicalis</i> isolates from two countries and one ATCC strain in a global context. Multilocus sequence typing (MLST) and single nucleotide polymorphism (SNP)-based phylogenies were generated. Minimum inhibitory concentrations (MIC) for antifungal agents were determined using Sensititre YeastOne YO10. Eleven (13.2%) isolates were fluconazole-resistant and 17 (20.5%) were classified as fluconazole-non susceptible (FNS). Together with four Canadian isolates, the genomes of 12 fluconazole-resistant (18 FNS) and 69 fluconazole-susceptible strains were examined for gene mutations associated with drug resistance. Fluconazole-resistant isolates contained a mean of 56 non-synonymous SNPs per isolate in contrast to 36 SNPs in fluconazole-susceptible isolates (interquartile range [IQR] 46–59 vs. 31–48 respectively; <i>p</i> < 0.001). Ten of 18 FNS isolates contained missense <i>ERG11</i> mutations (amino acid substitutions S154F, Y132F, Y257H). Two echinocandin-non susceptible isolates had homozygous <i>FKS1</i> mutations (S30P). MLST identified high genetic diversity with 61 diploid sequence types (DSTs), including 53 new DSTs. All four isolates in DST 773 were fluconazole-resistant within clonal complex 2. WGS showed high genetic variation in invasive <i>C. tropicalis</i>; azole resistance was distributed across different lineages but with DST 773 associated with in vitro fluconazole resistance.