Date of Award

Fall 12-2012

Degree Type

Honors College Thesis

Department

Biological Sciences

First Advisor

Mohamed O. Elasri

Advisor Department

Biological Sciences

Abstract

Staphylococcus aureus is an important human pathogen that causes hospital and community-acquired infections (52). These infections are difficult to treat due to resistance to a wide range of antibiotics and spread of antibiotic-resistant strains (13, 52). S. aureus causes infection by regulation of accessory genes encoding for expression of factors contributing to virulence (9, 11, 12, 29, 34, 43, 45), including severe infection, biofilm formation, autolysis, and antibiotic resistance (4, 5, 7, 27, 56). Actually, extracellular DNA and nutrient release during autolysis has been shown to contribute to the ability of bacteria to form and maintain a biofilm as well as to the prevalence of resistant strains within a bacterial species (2). The purpose of this study was to determine the effect msa, a global virulence regulator recently discovered in S. aureus (49, 50), has on resistance to different cell-wall-active antibiotics. This study also attempted to generate an allelic replacement vector causing antibiotic susceptibility, confirming the previous finding by Bae and Schneewind (2008). Population analysis profiles (PAPs) of twelve different cell-wall-active antibiotics in wild-type and msa mutant versions of USA300 LAC strain showed msa conferred higher resistance to six antibiotics tested. This finding supported the presentation of msa as a novel regulation mechanism for autolysis and antibiotic resistance within S. aureus (47). Also, after transduction of LAC with the pKOR1 plasmid encoding for chloramphenicol (CAM) resistance, homologous recombination into the bacterial chromosome, and chromosomal excision and loss of pKOR1, successful growth of one colony susceptible to CAM was observed. According to our knowledge, this was only the second time allelic replacement without selection by antibiotic markers has been produced within the bacterial species.

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