Exploring the female genital tract mycobiome in young South African women using metaproteomics Original paper

What was studied?

This study examined the female genital tract mycobiome metaproteomics in young South African women, using shotgun liquid chromatography–tandem mass spectrometry to characterize fungal taxa and their functional activity. Across 123 vaginal swab samples, investigators identified 39 fungal genera and explored how fungal abundance, fungal protein expression, and functional biological processes shifted across bacterial vaginosis (BV) states. The metaproteomic workflow offered a protein-level window into fungal community behavior, enabling analysis of genus-level patterns, protein signatures, and microbial functions such as histone acetylation, membrane raft polarization, and glycolysis. The work also integrated fungal–bacterial correlations, cytokine profiles, vaginal pH, sexually transmitted infections, and Nugent scoring to build a detailed ecological picture of how fungal communities coexist with BV-associated dysbiosis.

Who was studied?

Participants were 123 HIV-negative South African women aged 16–22, enrolled from the WISH cohort in Cape Town. All were generally healthy, non-pregnant, and free from recent antibiotic exposure or unprotected sex. The population exhibited high BV and STI prevalence, reflecting the region’s epidemiological context. Lateral vaginal wall swabs were collected at two time points (baseline and nine weeks), with extensive metadata including Nugent score, cytokine and chemokine levels, vaginal pH, Chlamydia trachomatis infection, and presence of clue cells. These factors enabled ecological modeling of fungal communities within a clinically relevant, high-risk population.

Most important findings

Candida dominated the mycobiome (53.2% relative abundance), while Conidiobolus, Rhizopogon, and Malassezia were also prominent. BV-negative women showed markedly higher Candida abundance, whereas BV-positive women had enrichment of Malassezia and Conidiobolus proteins. Lower total fungal protein abundance correlated with increasing Nugent score, and BV-positive states exhibited elevated fungal glycolytic activity and increased proteasome-mediated catabolic pathways. In contrast, BV-negative states showed high levels of histone H4 acetylation and membrane raft polarization, processes linked to fungal transcriptional regulation and hyphal growth in Candida. Fungal–bacterial interactions were striking. Malassezia sympodialis positively correlated with BV-associated bacteria such as Gardnerella vaginalis and Prevotella species.
Candida species correlated positively with Lactobacillus crispatus, L. iners, and L. jensenii, supporting their association with an optimal vaginal microbiome. Negative correlations, particularly between M. sympodialis and L. crispatus, reflected competitive ecological dynamics.

Clinical drivers—Nugent score, pro-inflammatory cytokines, chemokines, vaginal pH, C. trachomatis, and clue cells-were all significantly associated with shifts in fungal community composition. Machine-learning classifiers identified key protein markers (notably Candida actin and Malassezia proteasome-associated proteins) capable of predicting BV state with high accuracy.

Key implications

This work demonstrates that fungal communities, though low in abundance, are ecologically and functionally intertwined with BV-associated dysbiosis. Candida appears to be a hallmark of a Lactobacillus-dominant ecosystem, whereas Malassezia and Conidiobolus may signal BV-associated disruption. Functional shifts—including glycolytic upregulation in BV—suggest changes in fungal metabolic behavior that may reinforce or respond to bacterial dysbiosis. Integrating fungal signatures into microbiome-based diagnostics may refine clinical insights into BV, STI susceptibility, and genital inflammation.

Citation

Gangiah TK, Alisoltani A, Potgieter M, et al. Exploring the female genital tract mycobiome in young South African women using metaproteomics.Microbiome. 2025;13:76. doi:10.1186/s40168-025-02066-1