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bioRxiv · 10.1101/2025.09.24.678373

Clinical Candida Lactobacillus Isolate Pairs Reveal Distinct Host-Pathogen Interactions in a Vaginal Epithelial Model

Almutawa, E. M.·Novak-Frazer, L.·Tank, R.·Bignell, E.·Richardson, R.
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Abstract

Vulvovaginal candidiasis (VVC) is a highly prevalent condition affecting up to 75% of women, yet the mechanisms underpinning the transition from asymptomatic colonisation by Candida albicans to symptomatic infection remain incompletely understood. VVC is hormonally driven and rare in young girls and postmenopausal women. A central challenge lies in dissecting the complex interplay between microbial communities, hormonal factors, and host epithelial responses. While C. albicans is part of the normal vaginal microbiota at low abundance, its morphogenic switch to the hyphal form is closely linked with pathogenicity. Concomitantly, the dominance of specific Lactobacillus species is known to modulate vaginal health, but their precise role in shaping host-pathogen interactions during VVC is unresolved. We hypothesised that clinical isolate pairs of C. albicans and Lactobacillus spp. may differ in their ability to drive host epithelial damage, and that hormonal signals such as estrogen may exacerbate these interactions. To test this, we developed an in vitro VVC model using human vaginal epithelial cell (VEC) monolayers co-cultured with clinical isolate pairs. Using LDH release as a marker of cytotoxicity, extracellular pH monitoring, and immunoassays of mitogen-activated protein kinase (MAPK) phosphorylation, we interrogated host responses across microbial conditions in the presence or absence of estrogen. Our findings demonstrate that two clinical isolate pairs exhibit divergent behaviours. Pair C (C. albicans 203 and L. gasseri 167) suppressed epithelial cytotoxicity and maintained acidic pH, while Pair D (C. albicans 205 and L. jensenii 172) enhanced host damage and did not acidify the environment. Morphological differences in C. albicans isolates correlated with MAPK activation profiles, supporting a phenotype-specific host response. These results reveal that strain-level interactions within the vaginal microbiota significantly modulate host-pathogen dynamics.

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Almutawa, E. M., Novak-Frazer, L., Tank, R., Bignell, E., Richardson, R.. 2025-09-24. Clinical Candida Lactobacillus Isolate Pairs Reveal Distinct Host-Pathogen Interactions in a Vaginal Epithelial Model. https://doi.org/10.1101/2025.09.24.678373

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