Regulation Of Staphylococcus Aureus Cell Envelope Autolysis And Lipid Composition

Staphylococci are diverse group of catalase-positive and –negative Gram-positive cocci and are found associated with humans and animals. Many of these cocci are pathogenic and cause a variety of infections ranging from superficial to systemic. This thesis covers an understanding of cell wall autolysis in targocil-exposed S. aureus, and various aspects of membrane biophysics of pigmented and non-pigmented S. aureus and some clinically relevant coagulase-negative staphylococci (CONS). Targocil is a novel antistaphylococcal agent that inhibits translocation of wall teichoic acid (WTA) polymer across the membrane. WTA is a cell wall component and influences activity of the major autolysin (Atl) in the cell envelope. Autolysins are enzymes required to remodel cell wall during cellular growth and division. In this study, untranslocated-WTA was proposed to hinder the Atl enzyme at the membrane resulting in a significant decrease in autolysis in the targocil-exposed S. aureus. The second chapter of this thesis analyzed interrelationships among fatty acid composition, staphyloxanthin content, fluidity and carbon flow in the S. aureus membrane. Staphyloxanthin is a characteristic triterpenoid membrane-associated golden pigment in S. aureus and has been reported to have role in maintaining membrane fluidity. The levels of pigmentation vary among various strains and under different environmental conditions in an incompletely understood manner. This study uncovered that the levels of staphyloxanthin were influenced more through metabolic regulation than responding to fatty acids incorporated into the membrane. The final chapter explored the growth environment-dependent plasticity of fatty acid composition in some clinically important CONS. CONS thrive in different skin sub-environments in human and animals and skin is known to have variety of antimicrobial fatty acids. Here, the CONS were observed to have distinctly different fatty acid compositions, membrane fluidities and response to the known antimicrobial fatty acids when grown in different growth conditions. The observations suggest that the underlying differences in their ability to synthesize de novo and/or acquire exogenous fatty acids might be due to adaptation at the skin sub-environmental habitat