Graduation Date

Spring 5-4-2024

Document Type


Degree Name

Doctor of Philosophy (PhD)


Interdisciplinary Graduate Program in Biomedical Sciences

First Advisor

Vinai C. Thomas

Second Advisor

Kenneth W. Bayles

Third Advisor

Paul D. Fey

Fourth Advisor

Matthew C. Zimmerman


Staphylococci, particularly Staphylococcus epidermidis, are common causes of implant-associated infections that may result in notable morbidity and mortality. One of the ways the innate immune system attempts to combat these invading pathogens is via the respiratory burst, in which free radical species such as nitric oxide (NO), toxic to bacterial respiration, are released in large quantities. Despite the toxicity of NO, some bacteria, including staphylococci, encode an endogenous bacterial nitric oxide synthase (bNOS), whose physiological role has been unclear until now. In this dissertation, we demonstrate that S. epidermidis is able to overcome the toxicity of NOby converting this NO to nitrite. Furthermore, this nitrite enhances S. epidermidis growth by actively reducing the production of harmful superoxide, generated by flavohemoglobin Hmp, via promotion of the regulatory CymR-CysK complex. In addition, NOS-dependent CymR-CysK regulation also serves to enhance growth by repressing the expression of polysaccharide intercellular adhesin (PIA) and preventing carbon redirection away from peptidoglycan biosynthesis. Together, these data demonstrate that the activity of bacterial NOS is critical in maintaining optimal growth and homeostasis of staphylococci.


2024 Copyright, the authors

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