ORCID ID
Graduation Date
Spring 5-4-2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Programs
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
Abstract
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 NO• by 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.
Recommended Citation
Singh, Ryan M., "The Physiological Significance of Nitric Oxide Synthase in Staphylococci" (2024). Theses & Dissertations. 801.
https://digitalcommons.unmc.edu/etd/801
Permission rights from Redox Biology journal for reprinting of published material
Included in
Bacteria Commons, Bacterial Infections and Mycoses Commons, Bacteriology Commons, Genetics Commons, Laboratory and Basic Science Research Commons, Microbial Physiology Commons, Organismal Biological Physiology Commons, Other Immunology and Infectious Disease Commons
Comments
2024 Copyright, the authors