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

Abstract

<SPAN style="font-weight: 400;">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 </SPAN><SPAN style="font-weight: 400;">Nakaseomyces glabrata </SPAN><SPAN style="font-weight: 400;">infection while the other three had </SPAN><SPAN style="font-weight: 400;">Candida albicans</SPAN><SPAN style="font-weight: 400;">. 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 </SPAN><SPAN style="font-weight: 400;">C. albicans</SPAN><SPAN style="font-weight: 400;"> 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. </SPAN>