The Role of the Nutrient Sensor CodY in Regulating Nuclease Production and Extracellular DNA Metabolism in Staphylococcus Aureus
Mlynek, Kevin D
Brinsmade, Shaun R
As an opportunistic pathogen, Staphylococcus aureus is a leading cause of skin and soft tissue infections. The success of S. aureus as a pathogen stems from its ability to produce a plethora of virulence factors that aid in nutrient acquisition and host immune evasion as well as adhesion and biofilm formation. Previous studies have shown that the global transcriptional regulator CodY integrates nutrient availability with the regulation of nearly all virulence genes in S. aureus, including those required for immune evasion and biofilm development. Furthermore, a growing body of literature suggests that extracellular DNA (eDNA) is a critical factor in biofilm development as eDNA both acts as a scaffold for biofilms and can be degraded to aid in the evasion of the host immune response during infection. The primary focus of my dissertation research has been to understand how the CodY protein integrates the nutritional status of the cell into eDNA utilization. My thesis provides two lines of evidence that CodY governs eDNA utilization as I discovered: (i) a novel regulatory pathway by which CodY regulates the production of secreted nuclease via the S. aureus exo-protein secretion system (Sae TCS) and (ii) that CodY mutants produce an eDNA dependent biofilm by using the secreted polysaccharide PIA as a molecular sponge. My dissertation work reveals a complex regulatory network where both intracellular and environmental signals are integrated through CodY to control pathogenesis in the human pathogen S. aureus.
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