A systems biology approach to identify host molecular signatures of genital Candida albicans infection – implications for sexual HIV transmission

Background: The fungal infection C. albicans is prevalent in the female genital mucosa and can cause symtomatic vulvovaginal candidiasis with intense mucosal inflammation.

Genital inflammation can increase the risk of sexual HIV transmission, as this mucosal site is the main portal of HIV entry. We here aim to reveal how vulvovaginal candidiasis affects mucosal molecular signatures of HIV susceptibility.

Work plan: Host molecular signatures in genital tissue and secretion samples will be identified in: a) a retrospective Kenyan cohort of C. albicans PCR positive cases, b) a prospective randomized clinical trial of an antifungal product in Swedish women with recurrent vulvovaginal candidiasis.

Systems biology techniques will be applied, including proteomics, bulk transcriptomics, imaging analysis and spatially resolved transcriptomics combined with in situ gene sequencing. Tissue samples will be further assessed by electron microscopy to explore vaginal biofilm formations.

The discovery phase will be followed by validation in a C. albicans-exposed ex vivo genital tissue explant model, including HIV challenge experiments.

Significance: This project will increase the understanding of how C. albicans affects the genital mucosa from an HIV susceptibility perspective.

It will also evaluate mucosal molecular effects of an antifungal compound in a prospective clinical trial aimed to decrease recurrency rates of genital C. albicans infections and reduce current antibiotic use.