Masters Theses

Date of Award

5-2025

Degree Type

Thesis

Degree Name

Master of Science

Major

Microbiology

Major Professor

Lindsey R Burcham

Committee Members

Lindsey Burcham, Erik Zinser, Andrew Monteith

Abstract

Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is a Gram Positive facultative anaerobe that generally persists in the gut and reproductive tract, and can become opportunistically pathogenic in immunocompromised hosts. To better understand GBS persistence and disease morphologies, we have investigated the peroxide responsive repressor (perR) in GBS, to allow for better characterization of this organism’s response to reactive oxygen species (ROS) stress and iron regulation mechanisms. PerR is a repressive regulator that has been characterized in other Gram-Positive organisms, but not in GBS. However, in GBS it has been identified in a murine vaginal colonization transposon library experiment as impactful for the purpose of persistence in that environment. Characterizing the role of perR in GBS will increase our understanding of how this catalase negative organisms response to reactive oxygen stress, and how the ROS response and iron homeostasis may interact. Using perR deletion strains, we showed that perR does act as a regulator of the peroxide stress response, as deletion strains show increased resistance to hydrogen peroxide. In a murine model of GBS vaginal colonization, perR depletion strains also showed a modest decreased colonization persistence compared to WT strains in CD-1 mice. PerR was also shown to play a role in iron regulation and homeostasis, as a deletion strain shows both increased sensitivity to iron chelation, and increased resistance to iron toxicity. Q-PCR was also used to identify several iron homeostasis genes, fetB and VIT, that are upregulated in a perR mutant background. Due to the role of GBS as an opportunistic pathogen in systemic disease, we also investigated the virulence of the perR mutant in a murine model of systemic disease. In this model, the mutant strain showed significantly decreased virulence compared to WT strains. Overall, in GBS perR has been characterized as being a driver of regulation for both peroxide stress and iron homeostasis, as well as a regulatory of certain virulence genes and phage elements.

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