Date Presented

Spring 5-2021

Document Type

Thesis

Degree Name

Bachelor of Science

Department

Biomedical Science

First Advisor

Jamie L. Brooks, PhD

Second Advisor

Ghislaine L. Lewis, PhD

Third Advisor

Beth Savage, PhD

Abstract

Women of African descent are more likely to develop bacterial vaginosis (BV) and bear twice the risk of preterm birth and the increased risk of other pregnancy complications. Sneathia amnii is a pathogenic anaerobe found in the female urogenital tract that is associated with adverse outcomes such as preterm birth, BV, and chorioamnionitis. S. amnii has been found at a greater prevalence in the vaginal microbiota of women of African ancestry, which links it to a potential role in the disparities observed in health outcomes for these women. S. amnii encodes the cytopathogenic toxin A (CptA), an exotoxin that perforates fetal membranes and lyses red blood cells. This study seeks to determine which domain of the cytotoxin (N or C-terminal) is responsible for the cytotoxic and hemolytic activity. Our work has revealed that the C-terminal domain is involved in binding to some host cell surface receptors and that the N-terminal domain is the pore-forming domain. Our work also found evidence that the C-terminal binding domain can competitively inhibit the cytolytic activity of full-length CptA, which suggests that the toxin binds to a specific receptor and that binding is saturable. Advances in our understanding of CptA and S. amnii pathogenicity will lead to a more educated approach to therapeutic intervention and may reduce health disparities in gynecologic and obstetric complications associated with the vaginal microbiome.

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