Date of Award

Spring 5-5-2023

Level of Access Assigned by Author

Open-Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Microbiology

Advisor

Melody Neely

Second Committee Member

Sally Malloy

Third Committee Member

Joshua Kelley

Additional Committee Members

Benjamin King

Deborah Bouchard

Keith Hutchinson

Abstract

Streptococcus agalactiae (Group B Streptococcus or GBS) is a common bacterium found in pregnant women that can cause severe infections in neonates. Although detecting maternal colonization and administering antibiotics during labor can prevent early-onset GBS disease in neonates, antibiotics negatively affect newborns' microbiota, leading to complications like gastrointestinal disorders and immune system dysregulation. Therefore, alternative therapeutic measures are necessary to improve maternal and neonatal outcomes. Understanding GBS disease pathology and developing effective preventive measures and treatments is essential. GBS evolves from a commensal bacterium to an invasive disease-causing pathogen using various mechanisms, such as adapting to the host immune response, utilizing virulence factors like surface proteins, and regulating gene expression. The GBS genome contains mobile genetic components, including prophages, plasmids, insertion sequences, and transposons, that facilitate mutations and lateral gene transfer. This adaptability allows GBS to develop new virulence factors and antibiotic resistance, enhancing its ability to cause disease and evade host defenses. Prophages, viral genomes that are integrated into bacterial genomes, may play a critical role in GBS evolution, and understanding their contribution to its virulence could lead to innovative treatments. Bioinformatic analysis of 49 clinical isolates of GBS identified 42 prophages present in their genomes, which can be classified into 5 clusters based on their genomic content, indicating differences in the genetic makeup of the prophages. Further investigation of a hypervirulent GBS strain, found that the only prophage present provides a competitive advantage to the bacterium, possibly by enabling it to better compete for nutrients or resist other bacterial species. The absence of the prophage leads to a metabolic shift, indicating its significant impact on bacterial metabolism and possibly on the pathogen's virulence. Overall, the findings from this dissertation highlight the importance of prophages in GBS pathogenesis and emphasize the need for further research to develop novel therapeutic approaches for the prevention and treatment of GBS infections.

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