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Population genomic analyses reveal evidence for limited recombination in the superbug Candida auris in nature.

ABSTRACT: Candida auris is a recently emerged, multidrug-resistant pathogenic yeast capable of causing a diversity of human infections worldwide. Genetic analyses based on whole-genome sequences have clustered strains in this species into five divergent clades, with each clade containing limited genetic variation and one of two mating types, MTL a or MTL α. The patterns of genetic variations suggest simultaneous emergence and clonal expansion of multiple clades of this pathogen across the world. At present, it is unclear whether recombination has played any role during the evolution of C. auris. In this study, we analyzed patterns of associations among single nucleotide polymorphisms in both the nuclear and the mitochondrial genomes of 1,285 strains to investigate potential signatures of recombination in natural C. auris populations. Overall, we found that polymorphisms in the nuclear and mitochondrial genomes clustered the strains similarly into the five clades, consistent with a lack of evidence for recombination among the clades after their divergence. However, variable percentages of SNP pairs showed evidence of phylogenetic incompatibility and linkage equilibrium among samples in both the nuclear and the mitochondrial genomes, with the percentages higher in the total population than those within individual clades. Our results are consistent with limited but greater frequency of recombination before the divergence of the clades than afterwards. SNPs at loci related to antifungal resistance showed frequencies of recombination similar to or lower than those observed for SNPs in other parts of the genome. Together, though very limited, evidence for the observed recombination for both before and after the divergence of the clades suggests the possibility for continuous genetic exchange in natural populations of this important yeast pathogen.

SUBMITTER: Wang Y

PROVIDER: S-EPMC9218166 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Candida auris has emerged globally as a multidrug-resistant yeast that can spread via nosocomial transmission. An initial phylogenetic study of isolates from Japan, India, Pakistan, South Africa, and Venezuela revealed four populations (clades I, II, III, and IV) corresponding to these geographic regions. Since this description, C. auris has been reported in more than 30 additional countries. To trace this global emergence, we compared the genomes of 304 C. auris isolates from 19 countries on six continents. We found that four predominant clades persist across wide geographic locations. We observed phylogeographic mixing in most clades; clade IV, with isolates mainly from South America, demonstrated the strongest phylogeographic substructure. C. auris isolates from two clades with opposite mating types were detected contemporaneously in a single health care facility in Kenya. We estimated a Bayesian molecular clock phylogeny and dated the origin of each clade within the last 360?years; outbreak-causing clusters from clades I, III, and IV originated 36 to 38?years ago. We observed high rates of antifungal resistance in clade I, including four isolates resistant to all three major classes of antifungals. Mutations that contribute to resistance varied between the clades, with Y132F in ERG11 as the most widespread mutation associated with azole resistance and S639P in FKS1 for echinocandin resistance. Copy number variants in ERG11 predominantly appeared in clade III and were associated with fluconazole resistance. These results provide a global context for the phylogeography, population structure, and mechanisms associated with antifungal resistance in C. auris IMPORTANCE In less than a decade, C. auris has emerged in health care settings worldwide; this species is capable of colonizing skin and causing outbreaks of invasive candidiasis. In contrast to other Candida species, C. auris is unique in its ability to spread via nosocomial transmission and its high rates of drug resistance. As part of the public health response, whole-genome sequencing has played a major role in characterizing transmission dynamics and detecting new C. auris introductions. Through a global collaboration, we assessed genome evolution of isolates of C. auris from 19 countries. Here, we described estimated timing of the expansion of each C. auris clade and of fluconazole resistance, characterized discrete phylogeographic population structure of each clade, and compared genome data to sensitivity measurements to describe how antifungal resistance mechanisms vary across the population. These efforts are critical for a sustained, robust public health response that effectively utilizes molecular epidemiology.

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Population genomic analyses reveal evidence for limited recombination in the superbug Candida auris in nature.

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