Date of Award

Fall 12-2008

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biological Sciences

Committee Chair

Dr. Mohammed Elasri

Committee Chair Department

Biological Sciences

Abstract

Staphylococcus aureus is an important pathogen causing life threatening diseases in humans. Previously we showed that msa modulates the activity of sarA (Staphylococcal accessory regulator), which is one of a major global regulator of virulence in S. aureus. The objective of this study is to characterize the role of msa (Modulator of SarA) in the global regulation of virulence in S. aureus. Structure and function predictions were done using several computational tools and approaches to understand the nature of msa. A novel S. aureus microarray meta-database (SAMMD) was designed and developed to compare and contrast other transcriptomes with msa transcriptome. msa and sarA transcriptomes were generated using the microarray technology. Phenotypic and molecular assays were performed to support microarray results. The results show that msa is a putative transmembrane protein, with three transmembrane segments, a distinct N-terminal cleavable signal peptide, four phophorylation sites (two outside and two inside the membrane) and a binding site in the cytoplasmic region. Microarray results and comparative transcriptome analysis using SAMMD showed that several genes regulated by msa are also regulated by sarA. Based on these results I hypothesize that msa is a novel signal transducer, which modulates the activity of genes involved in virulence in a sar/\-dependent manner, while modulating the activity of genes involved in metabolism in a sar-4-independent manner.

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