All ETDs from UAB

Advisor(s)

Megan Kiedrowski

Committee Member(s)

Carlos Orihuela
Do-Yeon Cho
Edward Swords
Jessica Scoffield
Michael Gray

School

Joint Health Sciences (Interdisciplinary)

Document Type

Dissertation

Department (new version)

Microbiology

Date of Award

9-11-2025

Abstract

Chronic rhinosinusitis (CRS) is a complex inflammatory disease affecting the upper respiratory tract (URT) for a large portion of the populace, leading to significant economic burdens. Staphylococcus aureus is considered as a significant contributor to CRS inflammation through the production of toxins regulated through quorum sensing (QS). Microbiome studies have characterized the microbial communities present in the healthy URT and in CRS. These studies show that the genus Corynebacterium is associated with the healthy URT, decreased in CRS, and has a negative correlation with S. aureus regardless of health status. A few studies have partially characterized a mechanism to explain this negative correlation, finding that Corynebacterium can antagonize S. aureus through its QS system. However, this is unable to account for the high abundance of S. aureus in the healthy URT or the low abundance of Corynebacterium in CRS. Chapter Two of this dissertation demonstrates how URT-relevant temperature differences can mediate a reduction in Corynebacterium fitness while increasing S. aureus growth. Using fluorescent Corynebacterium isolates from the CRS URT, we compare temperature-mediated growth differences for Corynebacterium species and S. aureus on nasal epithelial cells using an air-liquid interface co-culture model. We found that higher temperatures mimicking the CRS URT increased S. aureus growth whereas Corynebacterium colonization of cells was significantly decreased. Chapter Three discovered a novel function for QS-regulated S. aureus toxins, called phenol-soluble modulins (PSMs), to disrupt Corynebacterium aggregation and adherence to nasal epithelial cells. Using a microscopy-based aggregation assay, PSMs were identified as the putative inhibiting factor secreted by S. aureus. Corynebacterium viability and metabolism were not significantly altered, however, adherence to epithelial cells was significantly reduced when adding recombinant PSMs. Collectively, this work shows how URT-relevant temperature differences and CRS-associated S. aureus toxins produced early in quorum-sensing activation can antagonize Corynebacterium species. These findings partially fill the gaps in knowledge for why Corynebacterium is decreased in the CRS microbiome and provide evidence explaining for the evolutionary pressure resulting in some Corynebacterium species’ capability to inhibit S. aureus quorum sensing.

Available for download on Thursday, September 10, 2026

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