Date of Award

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 wide variety of diseases ranging from chronic biofilm associated infection to acute life threatening infection such as bacteremia, pneumonia, osteomyelitis, or endocarditis, despite the progress with antibiotics used in the treatment of bacterial infections. Furthermore, increased use of prosthetic and indwelling devices in modern medical practices has led to increased infections due to S. aureus. Treating S. aureus infections have become difficult owing to its ability to resist most of the antibiotics; this problem is further exacerbated by ability of MRSA strains to form biofilms. Emergence of community-acquired methicillin resistance staphylococcus aureus (CA-MRSA) strains that cause severe infection among the healthy individual with no predisposing factor further exacerbate the conditions.

CA-MRSA strains produce a vast array of virulence factors that are controlled by a complex network of global virulence regulators, and they make this pathogen more successful compared to other MRSA strains. In previous study, we have shown that the msaABCR is a new four gene operon that globally regulates virulence and biofilm development in S. aureus. Also we have shown that this operon regulates the expression of some well-characterized global regulators like sarA and agrA which play vital roles in S. aureus pathogenesis. In order to study the role of individual gene in this operon, we deleted the first gene (msaA) of msaABCR operon and found that msaA gene plays an opposing role in the regulation of msaABCR operon in terms of regulation of sarA, extracellular protease production, and biofilm formation. Deletion of msaA led to the over-expression of sarA, decreased protease production, and increased biofilm formation, which is in contrast to msaC and msaABCR deletion mutant which down regulates the expression of sarA, increases the production of protease, and decreases biofilm formation, which suggests a regulatory role for msaA gene in regulation of msaABCR operon.

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