Graduation Date

Fall 12-17-2021

Document Type


Degree Name

Doctor of Philosophy (PhD)


Pathology & Microbiology

First Advisor

Ken Bayles


Staphylococcus aureus is a metabolically versatile human pathogen, causing disease in many areas of the body. Its versatility can be attributed to the fact that it utilizes a variety of tools to adapt to many different environments, including toxins to scavenge from the host and multiple transporters to compete for its preferred carbon sources. S. aureus can also survive in harsh conditions through biofilm development, which are notoriously recalcitrant to antibiotics and immune defenses. Biofilms exhibit marked heterogeneity, with division of labor for production of matrix components and differential gene expression among various niches within the biofilm.

In this study, we investigated the development of metabolic heterogeneity as structures form during biofilm maturation. Additionally, we investigated how metabolic regulators control proper development of mature structures and their impact on biofilm matrix composition. We observed the initiation of metabolic heterogeneity before nutrient gradients could form within structures, consistent with recent findings that heterogeneity is a trait that begins from the first stages of biofilm development, when cells encounter a surface. Furthermore, we observed inactivation of CodY and CcpA have a substantial impact on central carbon and nitrogen metabolism as well as toxin production and biofilm development.