Migration and standing variation in vaginal and rectal yeast populations in recurrent vulvovaginal candidiasis

Vulvovaginal candidiasis is a very common human fungal infection. Most are successfully treated with antifungal drugs, yet ~8% lead to recurrent vulvovaginal candidiasis (RVVC). Vaginal and rectal populations have been previously found to be closely related in RVVC. Yet the genomic methods used precluded the assessment of fine-scale relationships and the measurement of within-population variation, a fundamental property with evolutionary implications. To address this gap, we isolated 12 vaginal and 12 rectal yeast isolates from four individuals with a history of RVVC. Three individuals had Candida albicans infections, while the fourth had Nakaseomyces glabratus. All isolates were whole-genome sequenced and phenotyped. Isolates were placed into species-level phylogenies composed of isolates from many different countries and contexts, including an updated N. glabratus tree with over 500 isolates. Genotypic and phenotypic analyses were consistent with migration between sites. There was little phenotypic diversity in drug response and no consistent difference between isolates from different sites for invasive growth. Although there are few comparables, C. albicans nucleotide diversity was similar to most commensal oral and rectal populations, while N. glabratus was similar to some bloodstream infections (though higher than others). Single-nucleotide changes drove intra-population genetic differences; only a single loss-of-heterozygosity tract varied among isolates from within one participant. This study provides baseline measurements and describes techniques to quantify within-population diversity in fungal microbes. We highlight a need for comparable studies that use the same sampling effort and analysis methods to understand the interplay between evolutionary factors in shaping fungal microbial communities.

Vaginal yeast infections are very common, yet we do not understand why some people experience chronic infections when most have a single infection that is successfully treated and cleared. We examined 12 vaginal and 12 rectal yeast isolates from four individuals with a history of recurrent yeast infections (total 96 isolates). Three participants had a Candida albicans infection (the most common causative species), while the fourth had a Nakaseomyces glabratus infection (the second most common and increasingly implicated). We found that vaginal and rectal isolates were closely related genetically, indicating the same population is present at the two sites. Surprisingly, we found that diversity was similar to the yeast populations found at other body sites in healthy people. Our study highlights a critical need for additional studies following the same methods in different contexts to better understand the fungal microbial populations in our bodies.