Membrane Stress Resistance Mechanisms In Bacillus Subtilis

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Bacteria exist in environments that can inflict a variety of stresses upon the cell, many of which target the cell membrane. As a result, bacterial survival often depends upon the ability of cells to adjust the cell membrane in response to environmental stress. This process is controlled by the cell envelope stress response (CESR), the signal transducing regulatory systems that allow cells to sense and respond to conditions that perturb the cell wall or membrane. In Bacillus subtilis, a major component of CESR is controlled by extracytoplasmic function sigma (ECF [SIGMA] factors. Numerous studies have associated ECF [SIGMA] factors with membrane stress adaptations, but the specific details concerning the effects of particular [SIGMA] factors on membrane composition and the underlying mechanisms involved are largely unknown. Here, we investigate these details using B. subtilis as a model system. The majority of this work consists of two main projects. In one project, I characterized a novel homeoviscous adaptation in which an ECF  promoter modifies fatty acid composition by regulating the membrane biosynthesis genes fabHa and fabF. The altered expression of these genes leads to a greater proportion of straight chain fatty acids in the membrane and an increase in average fatty acid chain length. Such changes in the lipid profile of B. subtilis reduce membrane fluidity thereby conferring resistance against detergents and antimicrobial compounds produced by competing Bacillus strains. The second project focuses on ECF  factor-mediated lantibiotic resistance mechanisms in B. subtilis. I've identified six distinct lantibiotic resistance loci activated by ECF [SIGMA] factors. These loci include genes encoding phage shock proteins, tellurite resistance related proteins, signal peptide peptidase, and proteins that synthesize and modify teichoic acids. My work has made substantial progress on defining the resistance mechanisms associated with these genes.
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cell envelope stress response; extracytoplasmic function sigma factors; antibiotic resistance
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Helmann, John D
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Alani, Eric
Winans, Stephen C
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Ph. D., Biochemistry
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Doctor of Philosophy
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Government Document
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dissertation or thesis
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