Dynamics of the Vaginal Micro- and Mycobiota in Women with Vulvovaginal Candidiasis
AdvisorRavel, Jacques, Ph.D.
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AbstractVery little is known about the dynamics of the vaginal micro- and mycobiota and interactions between fungal and bacterial species, especially as it relates to vulvovaginal candidiasis (VVC). VVC is most often caused by Candida albicans and is one of the most common types of infectious vaginitis. The central hypothesis of this work is that the vaginal communities of bacteria and fungi, the microbiota and mycobiota, respectively, serve as an active ecological barrier to the invasion of Candida species. We predict that changes in composition and/or abundance of these populations enable Candida's evasion of microbial defenses and infection of the mucosa. Next-generation sequencing and quantitative PCR of the 16S rRNA gene and ITS1 region of 18S rRNA gene within vaginal samples collected in a 10-week daily-sampling prospective longitudinal study were used to explore changes in microbial community composition and abundance in women who developed VVC. The microbiota clustered into 9 bacterial community state types (CST) and the mycobiota clustered into 3 fungal community state types (fCST). Samples collected before VVC are most often associated with non-Lactobacillus (CST IV) communities, but in the days immediately prior to reported symptoms there is a decrease in alpha diversity and increase in community stability. Though many fungal taxa, including Malassezia, Emericella, and Alternaria, are abundant before and after VVC, Candida is dominant during active infection. Changes in absolute abundances of bacterial and fungal taxa within the micro- and mycobiota are affected by host behaviors, including sexual activities, contraceptives, and hygiene practices. There is a statistically significant decrease in the ratio of total bacterial to total fungal load in the transition before and during VVC. A comparative genomics analysis of C. albicans isolates from women with VVC highlights the genetic relatedness of vaginal strains and points to genomic microvariations that may play a role in Candida commensalism, leading to asymptomatic colonization, and pathogenesis, resulting in VVC. Taken together, these findings suggest that changes in composition and abundance of the vaginal micro- and mycobiota, as well as genetic characteristics of the pathogen, contribute to a woman's susceptibility to develop an infection by Candida spp.
DescriptionUniversity of Maryland, Baltimore. Molecular Microbiology and Immunology. Ph.D. 2017