Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Microbiology and Immunology

Supervisor

McGavin, Martin J.

Abstract

The success of the USA300 strain of methicillin resistant Staphylococcus aureus can be attributed in part to its enhanced ability to overcome innate defenses of the skin including sebum, which provides a source of antimicrobial unsaturated free fatty acids (uFFA). We have previously identified farE and farR genes that confer S. aureus resistance to uFFA, respectively encoding a uFFA efflux pump and a TetR family regulator required for farE expression. However, the exact regulatory mechanism of FarR remains to be elucidated. Here, we show the importance of a conserved TAGWTTA motif in FarR operator sites, such that the loss of this motif in autoregulatory operator sites caused a de-repression of FarR. However, this de-repression did not cause an increase in resistance to uFFA. Additionally, we have identified the importance of cysteine residues for FarR function. These findings shed further light on the mechanisms of S. aureus resistance to antimicrobial uFFA.

Summary for Lay Audience

Staphylococcus aureus colonizes approximately 30% of the population asymptomatically and yet can cause mild to severe infections. Frequently, these infections are caused by the colonizing strain. Therefore, understanding the mechanism by which S. aureus persists on, and colonizes the skin is of importance. USA300 is the predominant strain of community acquired methicillin resistant S. aureus in North America and is the leading cause of skin and soft tissue infections. The success of USA300 can be attributed in part to their enhanced ability to overcome the immune defences of the skin, which include fatty acids that are found in the sebum. These fatty acids are toxic and therefore, USA300 employs several strategies to overcome this toxicity. One way is through the removal of fatty acids from the bacterial cell through the protein FarE. Here, we further study the regulation of FarE by its regulator, FarR. Overall, these findings shed further light into fatty acid resistance strategies employed by S. aureus.

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