Genotypic and phenotypic homogeneity of vaginal and rectal yeast isolates from recurrent vulvovaginal candidiasis

Vulvovaginal candidiasis is one of the most common vaginal and fungal infections. Many are successfully treated with antifungal drugs, but ∼9% of cases will recur even with treatment (RVVC). We quantified the genotypic and phenotypic diversity of vaginal and rectal yeast isolates from four individuals with a history of recurrent vulvovaginal candidiasis during a symptomatic relapse. One participant had a Nakaseomyces glabrata infection while the other three had Candida albicans . We used whole genome sequencing to place the isolates into a global phylogenic context and precisely quantify standing genetic variation within RVVC yeast populations. The C. albicans isolates statistically clustered close together and closer than expected to other vaginal isolates in a subgroup of clade 1. In all participants, we found that vaginal and rectal isolates are monophyletic and phylogenetically overlapping, consistent with frequent migration between sites. We found very low levels of genotypic and phenotypic diversity and few phenotypic outliers, consistent with rapid population expansion. This provides a view of the within-host isolate variation that is inconsistent with a rectal source population for vaginal reinfection and a generally small effective population size over time in RVVC. Importance Recurrent vaginal yeast infections are relatively common, yet many open questions remain about the infecting fungal population. We examined the genetic and phenotypic diversity within vaginal and fungal populations from four individuals with a history of recurrent yeast infections experiencing symptoms. Three of the participants had a Candida albicans infection (the most common causative species) while the fourth had a Nakaseomyces glabrata infection (the second most common and increasingly implicated). This is the first study to use whole genome sequencing to capture genotypic diversity within recurrent yeast infections precisely. We found that vaginal and rectal isolates were overlapping, indicating frequent migration of individuals between the two sites. The overall level of genetic variation within the populations was very low and nearly all isolates had very similar phenotypes. These results are consistent with rapid population expansion during symptomatic infection and inconsistent with a rectal source population leading to vaginal reinfection.