Impact of the mycobiome on the health of the female genital tract

Gangiah, Tamlyn Kirstey

Impact of the mycobiome on the health of the female genital tract

Master Thesis

2022

Abstract

The female genital tract microbiome comprises a community of microorganisms. Imbalances in the microbiome are associated with vaginal diseases such as bacterial vaginosis (BV) and sexually transmitted infections (STIs). These diseases greatly burden South Africa, and young women in this region are at an increased risk of contracting vaginal diseases. Consequently, it is vital to investigate the factors that influence FGT health. The fungal constituent of the microbiome (the mycobiome) has been demonstrated to play a role in regulating mucosal health, especially when the bacterial component is disturbed. However, we have a limited understanding of the vaginal mycobiome since many microbiome studies have focused on bacterial communities and have neglected low abundance taxonomic groups, such as fungi. To reduce this knowledge deficit, we present the first large-scale metaproteomic study to define the taxonomic composition and potential functional processes of the vaginal mycobiome in South African women. We examined vaginal fungal communities present in optimal and nonoptimal states (BV, STIs, and genital inflammation) by collecting lateral vaginal wall swabs from 123 women for liquid chromatography-tandem mass spectrometry. Taxonomic analysis requires representative sequence databases; however, since mycobiome research is relatively new, fungal databases are still in their infancy. As a result, metaproteomic methods are not optimized for fungal research. Therefore, we optimized a metaproteomic approach to increase fungal protein group assignments. With this, 50 fungal proteins belonging to 39 different genera were identified post quality-control and analysed for taxonomic and functional distributions. Taxonomic analysis revealed that the vaginal mycobiome had a high relative abundance of Candida across optimal and non-optimal states. We observed changes in differential abundance at the genus and biological process level between optimal and non-optimal states for BV and Mycoplasma genitalium. In the BV positive state, most fungal proteins were significantly underabundant (p< 0.05) compared to the BV negative state, with the exception of Malassezia and Condiobolus. Correspondingly, Nugent score was negatively associated with total fungal protein intensity, implying that the microenvironment during BV is less suitable for fungal growth. Furthermore, we assessed which clinical variables were associated with driving fungal community composition; results indicated that Nugent score, pro-inflammatory cytokines, chemokines, vaginal pH, Chlamydia trachomatis, and the presence of clue cells were involved. Lastly, we used publicly available vaginal proteome data to confirm our fungal identifications and suspect Candida, Debaryomyces, Kluyveromyces, Malassezia, Penicillium, Yarrowia, Aspergillus, Cryptococcus, Wallemia, Trichosporon, and Saccharomyces are likely true vaginal inhabitants. Thus, this study sets the groundwork for understanding the vaginal mycobiome and its association with prevalent vaginal diseases.

Keywords

Bioinformatics

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