Date of Award

9-30-2015

Document Type

Thesis and Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

School of Biological Sciences

First Advisor

Craig Gatto

Second Advisor

Brian J. Wilkinson

Abstract

The cytoplasmic membrane of bacterial cells, forming an essential barrier from the surroundings, is a critical component of cellular physiology ensuring proper survival and maintenance of major cellular functions. The integrity of the membrane is an important feature that plays an essential role in the transport of solutes and nutrients through active and passive pathways, functions of membrane-associated proteins, electron transport and ATP synthesis, maintaining turgor pressure and combating environmental stresses, and thus is a crucial factor of a majority of cellular adaptations. The various biophysical properties affecting the integrity of this membrane are mainly determined by the composition and proportion of the fatty acyl residues of membrane phospholipid backbone which are subject to dynamic changes in response to the external environment to regulate the ideal fluidity/viscosity of the membrane. This enables the bacteria to adapt to changing environments. Additionally, membrane fatty acid composition has a major influence on bacterial pathogenesis and virulence, susceptibility to antimicrobials and broader aspects of bacterial physiology. Gram-positive bacterial membranes are made mostly of varying proportions of straight-chain andbranched-chain fatty acids distributed on the phosphatidyl glycerol molecules along with unsaturated fatty acids in some cases.

Membrane fatty acid biosynthesis that determines this lipid composition has gained attention over recent years as a novel and efficient target for therapeutic agents. A key to study the dynamics of the membrane and its relation to the bacterial physiology is to design successful tools to induce or study alterations, native or novel, to the lipid composition and analyze the resulting consequences on major cellular attributes. This thesis describes the studies of the membranes of two major gram- positive bacterial pathogens, Listeria monocytogenes and Staphylococcus aureus, both posing a threat to human health due to either unsuccessful containment or rapid antibiotic resistance acquirement. The first chapter describes the modulations in the membrane composition of Listeria monocytogenes, a psychrophilic bacterium, through chemical supplementation which results in novel fatty acids by non-native enzymatic reactions and the consequences on the bacterial physiology. The second chapter outlines the versatility of Staphylococcus aureus membrane fatty acid composition in differencing growth environments, in vitro or in vivo. The following research will contribute a better understanding of fundamental membrane biophysical parameters in these bacterial pathogens that has been the target for novel drugs for a decade now, along with providing knowledge to support the intensive search for newer and more effective infection control strategies.

KEYWORDS: Membrane fatty acid composition, membrane fluidity, physiology, virulence, etc.

Comments

Imported from ProQuest Sen_ilstu_0092E_10628.pdf

Page Count

77

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