Date of Award

Summer 8-2014

Degree Type

Masters Thesis

Degree Name

Master of Science (MS)

Department

Biological Sciences

Committee Chair

Mohamed O. Elasri

Committee Chair Department

Biological Sciences

Committee Member 2

Glenmore Shearer

Committee Member 2 Department

Biological Sciences

Committee Member 3

Shahid Karim

Committee Member 3 Department

Biological Sciences

Abstract

Staphylococcus aureus is an important human pathogen that causes a wide variety of life-threatening infections ranging from minor skin and oral infections to severe infections, such as bacteremia, pneumonia, osteomyelitis, or endocarditis due to the presence and secretion of a large number of virulence factors that are controlled by global virulence regulators in complex networks. Furthermore, S. aureus infections have become a threat to public health because of their high potential to form biofilm, and their ability to resist a wide range of antibiotics has exacerbated further. Therefore, understanding the regulatory networks and developing a drug targeting these networks has the potential to stand as therapeutic targets for future treatment of antibiotic resistant infections.

In a previous study msaC was identified as the modulator of sarA, a new global virulence regulator that controls the expression of sarA and biofilm development. Furthermore, it has also been shown that msaC is a part of four-gene operon, msaABCR operon, which includes four-genes: SAUSA300_1296 (msaA), SAUSA300_1295 (msaB), SAUSA300_1294 (msaC), and antisense RNA, msaR. The mechanism of regulation of msaABCR operon and the function of individual genes were not clearly known yet. This study defines the role of msaB, the second gene of the msaABCR operon, which will help shed some light on the regulation of msaABCR. We deleted msaB gene from USA300_LAC, and studied the major msaB phenotypes: pigmentation, protease production, biofilm formation, and rate of cell death. Deletion of msaB resulted in the similar msaC and/or msaABCR deletion mutant, thus showing the importance of this gene in this operon. The mutant showed decreased pigmentation, increased extracellular protease production, decreased biofilm formation, and increased rate of cell death. Deletion of the msaB gene also resulted in the decreased expression of some key regulators, like sarA and agr that play major roles in the regulation of virulence and biofilm formation in S. aureus, similar to msaC and msaABCR operon deletion mutant.

Thus, this study identifies the role of msaB, in the msaABCR operon, that will help us define the mechanism of regulation of virulence and biofilm formation by the msaABCR operon and provides a step to investigate the stimulatory signals that the msaABCR operon responds to during pathogenesis.

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