Exploring the role of oestrogen in controlling the pathogenicity of Candida Albicans

Kumwenda, Pizga ORCID: 0000-0002-5475-3142 (2022). Exploring the role of oestrogen in controlling the pathogenicity of Candida Albicans. University of Birmingham. Ph.D.

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Abstract

Candida albicans is an opportunistic human pathogen capable of causing mild to serious invasive infections in almost all human organs and tissue. Sex hormones are generally known to render the host susceptible to Candida infections due to their ability to regulate host immunity. For instance, oestrogen is a well-recognised risk factor for Vulvovaginal candidiasis (VVC). Uptake of oral contraceptives, pregnancy and hormone replacement therapy raises circulatory concentration of oestrogen thereby promoting VVC. Nevertheless, the mechanism behind the influence of oestrogen on VVC is unclear. The present study investigated how adaptation of C. albicans to oestrogen influences the fungal host-pathogen interaction. C. albicans adaptation to physiologically relevant concentrations of oestrogen led to reduced immune recognition, and enhanced virulence. This was facilitated via inhibition of opsonophagocytosis through increased recruitment of Factor H (FH) and complement components on fungal cell surface. Acquisition of FH and complement components occurred via Glycerol-3-Phosphate Dehydrogenase 2 (Gpd2), a C. albicans moonlighting protein. Oestrogen enhanced expression of GPD2 through a non-canonical signal transduction pathway involving Bcr1. Thus, apart from rendering the host susceptible to VVC, oestrogen predisposes women to the infection by directly promoting fungal pathogenicity. Findings from this study may provide an opportunity to determine mechanisms behind gender-based predispositions to fungal infections and offer alternative strategies to improving health in women.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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