Identifying molecular signals in the female genital tract mucosa that determine susceptibility to sexually transmitted infections

The impact of sexually transmitted infections (STIs) on sexual and reproductive health in resource-limited settings is profound.

To limit the high mortality and morbidity caused by STIs there is an urgent need to develop preventive and therapeutic interventions against these infections.

One of the most significant correlates of increased susceptibility to STIs in women is being colonized with a polymicrobial anaerobic cervicovaginal microbiome.

During 2022-2024, we aim to identify mechanisms of host susceptibility to STIs that can inform us on preventive measures as well as drug targets.

Genital tissue samples from African women being colonized with a non-optimal (STI-risk associated) microbiome will be compared to samples representing a healthy Lactobacillus-dominated microbiome.

Gene expression patterns in the samples associated to the various microbiome compositions will be unravelled by spatial transcriptomics and in situ sequencing.

This discovery phase will be followed by validation of the gene expression patterns in an ex vivo genital tissue explant model.

As a proof-of-concept for the link between the identified molecular mechanisms and susceptibility to STIs, tissue explants representing various microbiome compositions will be challenged with infectious virus isolates.

Strengthening the genital epithelial barrier as well as modulating signaling pathways and immune functions with novel compounds would be important advances to prevent and treat STIs.