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Investigating the molecular mechanisms of pathogenic Group B Streptococcus interactions with fungus Candida albicans

Bristol student theses: Doctoral ThesisDoctor of Philosophy (PhD)

Authors

  • Grace Pidwill

Research units

Abstract

Group B Streptococcus (GBS) is the leading cause of neonatal sepsis and meningitis in developed countries. In the majority of cases, GBS is vertically transmitted from the mother during or preceding birth. Candida albicans is an opportunistic fungal pathogen of the female GU tract, causing vaginal thrush, for which pregnancy is a risk factor. As C. albicans is known to synergistically interact with Streptococcus bacteria within the oral cavity, it was hypothesised
that C. albicans and GBS may interact within the vaginal tract. Using a vaginal epithelial cell association assay, it was shown that C. albicans significantly promoted GBS association with vaginal epithelial cells (VECs) and, likewise, GBS significantly promoted C. albicans. The AgI/II family surface-expressed adhesins of GBS, designated Bsp proteins, were found to contribute to GBS interactions with VECs and with C. albicans, while the C. albicans cell surface protein Als3 was pivotal for the coassociation between these species. Investigations into the VEC
response to GBS and C. albicans implied that coassociation may reduce neutrophil chemotaxis, despite enhanced transcription of proinflammatory cytokine genes. Proteomics studies revealed that extracellular matrix (ECM) components, or proteins that modulate ECM components, were significantly elevated in dual-species-infected VECs, while apoptosis related proteins and proteins involved in MAPK signalling were largely downregulated. Taken together, these data suggest that GBS and C. albicans synergistically interact in a manner that
could promote GU tract colonisation and persistence, and that this coassociation is dependent on C. albicans Als3 and partially dependent on GBS Bsp proteins.

Details

Original languageEnglish
Awarding Institution
Supervisors/Advisors
Award date7 May 2019

    Research areas

  • Microbiology, Polymicrobial, Co-association, Group B Streptococcus, Candida albicans

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