Potential Signaling Mechanisms for the SaeR/S Two-Component System in Staphylococcus aureus

Owen Burroughs (1), Tyler Nygaard (1), Kyler Pallister (1), Jovanka Voyich (1)* (1)Department of Microbiology and Immunology, Montana State University: 109 Lewis Hall, Bozeman, Montana, 59717-3520 *Faculty Sponsor

Staphylococcus aureus (S. aureus) is a common and commensal human pathogen, causing conditions that range from mild soft-tissue infections to severe, life-threatening conditions such as necrotizing pneumonia and toxic shock syndrome. Successful S. aureus infection relies on the bacteria’s ability to detect and evade the host’s innate immune response, the first component of which is mounted by polymorphonuclear leukocytes (PMNs). To do this, S. aureus uses a variety of two-component systems to sense host PMNs and respond by up-regulating virulence factors such as leukotoxins and hemolysins. One such system, the SaeR/S two-component system, is particularly important for effective evasion of the host’s immune response. SaeR/S is comprised of SaeS, a trans-membrane histadine kinase, and SaeR, a response regulator. Upon activation by PMN components, SaeS phosphorylates the Asp51 residue of SaeR, allowing the protein to up-regulate a number of key virulence factors. My research looks to address the mechanism with which SaeS phosphorylates SaeR by measuring the virulence of different single amino acid mutants of S. aureus. Thus far, my data have shown the His132 residue of SaeS to be the active site for phosphorylation of SaeR—replacing this residue with alanine results in a significant decrease in virulence. In a knockout model lacking the entirety of SaeS, however, hemolysis is not significantly different than wild-type hemolysis. Taken together, this indicates that SaeR is also phosphorylated by a mechanism independent of SaeS, and that SaeS likely participates in phosphatase activity of SaeR. My project addresses this hypothesis using virulence assays such as measuring sheep’s blood hemolysis, as well as measuring lysis and activation of freshly purified human PMNs. A better understanding of the mechanisms that regulate the interaction of SaeS with SaeR may lead to the development of novel therapeutics to treat S. aureus infection.

Additional Abstract Information

Presenter: Owen Burroughs

Institution: Montana State University

Type: Oral

Subject: Biology

Status: Approved

Time and Location

Session: Oral 10
Date/Time: Wed 1:30pm-2:30pm
Session Number: 1004
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