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University of Rochester

1. Favazzo, Lacey Jane. Nitric Oxide Metabolism in CC30 Staphylococcus aureus and its Contribution to Virulence.

Degree: PhD, 2020, University of Rochester

Staphylococcus aureus is a pathogen that causes a wide spectrum of disease, of which the site of infection and level of persistence depend largely on different virulence traits encoded within genetically distinct lineages, called clonal complexes (CC). Differences in bacterial response to host immune factors also play a role. Activated phagocytes produce nitric oxide (NO) to control infection and S. aureus metabolically adapts via multiple strategies conserved in all CCs, including S. aureus nitric oxide synthase (Nos). Genomic analysis of the CC30 lineage suggests that it has acquired additional metabolic functions that support persistence and colonization patterns associated with chronic and severe infections, such as endocarditis and osteomyelitis. CC30 strains encoded a putative NO reductase (Nor) that is not found in other clonal complexes, which potentially contributes to NO resistance and clinical outcome. In this work, we demonstrate that Nor has true nitric oxide reductase activity. Expression of nor is enhanced by both anaerobic growth and NO stress. Additionally, we demonstrate that MgrA and SrrAB, which modulate S. aureus virulence and response to hypoxia, regulate nor. S. aureus nos is also regulated by these systems, suggesting a link in metabolic response between the two genes. RNA-Seq analysis of UAMS-1, UAMS-1 Δnor, and UAMS-1 Δnos under anaerobic growth and NO stress demonstrates that Nor contributes to nucleotide metabolism and Nos to glycolysis. We find that both Nos and Nor contribute to bacterial survival in the presence of human PMNs and that each displays organ specific seeding in a tail vein model of infection. Nor also contributes to abscess formation in an osteological implant model of infection. The regulation overlap between nor and nos point to an intriguing link between regulation of endogenous NO, metabolic adaptation, and persistence in the CC30 lineage.

Subjects/Keywords: Staphylococcus aureus; nitric oxide; CC30; metabolism; virulence.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Favazzo, L. J. (2020). Nitric Oxide Metabolism in CC30 Staphylococcus aureus and its Contribution to Virulence. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/35548

Chicago Manual of Style (16th Edition):

Favazzo, Lacey Jane. “Nitric Oxide Metabolism in CC30 Staphylococcus aureus and its Contribution to Virulence.” 2020. Doctoral Dissertation, University of Rochester. Accessed April 09, 2020. http://hdl.handle.net/1802/35548.

MLA Handbook (7th Edition):

Favazzo, Lacey Jane. “Nitric Oxide Metabolism in CC30 Staphylococcus aureus and its Contribution to Virulence.” 2020. Web. 09 Apr 2020.

Vancouver:

Favazzo LJ. Nitric Oxide Metabolism in CC30 Staphylococcus aureus and its Contribution to Virulence. [Internet] [Doctoral dissertation]. University of Rochester; 2020. [cited 2020 Apr 09]. Available from: http://hdl.handle.net/1802/35548.

Council of Science Editors:

Favazzo LJ. Nitric Oxide Metabolism in CC30 Staphylococcus aureus and its Contribution to Virulence. [Doctoral Dissertation]. University of Rochester; 2020. Available from: http://hdl.handle.net/1802/35548

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