The Response of Staphylococcus aureus to Culture in a Low-Fluid-Shear Environment

dc.contributor.advisorOtt, C. M.
dc.contributor.committeeMemberNickerson, Cheryl A
dc.contributor.committeeMemberWood, Thomas G
dc.contributor.committeeMemberTorres, Alfredo G
dc.contributor.committeeMemberNiesel, David W
dc.creatorCastro, Sarah 1983- 2012
dc.description.abstractThe opportunistic pathogen, Staphylococcus aureus, encounters a wide range of fluid shear levels within a human host. As an intestinal colonizer, S. aureus experiences the low-fluid-shear levels consistent with the site; however, as the intestinal presence of the organism is infrequently associated with disease, very few investigations have examined how this environmental parameter impacts the lifecycle of the bacteria. Therefore, the responses of S. aureus to culture in this environment were documented by means of the physiologically-relevant, low-fluid-shear conditions generated by the rotating-wall vessel bioreactor. Exposure to the low-shear environment initiated the formation of a novel attachment-independent biofilm in which the S. aureus cells were completely encased in an extracellular matrix that conferred increased antibiotic resistance. Further analysis of the cells within the biofilm revealed a decrease in carotenoid pigmentation and growth, an increase in susceptibility to oxidative stress, and increased killing by whole blood as compared to controls. In addition, low-shear-cultured S. aureus displayed increased macrophage clearance and a decreased ability to invade epithelial cells. Whole genome microarray analysis revealed that low-shear-cultured responsive genes were associated with fermentative respiration, consistent with the metabolic profile of S. aureus within a biofilm. Additional molecular investigations revealed the decreased expression of the RNA chaperone gene, hfq, which parallels the low-shear response of certain Gram-negative microorganisms. This is the first report describing an Hfq association with fluid shear in a Gram-positive organism, indicating that the ability to sense and respond to mechanical stimuli is evolutionarily-conserved among structurally diverse prokaryotes. Collectively, these findings demonstrate the ability of low fluid shear to serve as an environmental cue directing S. aureus toward a colonization phenotype in which it decreases known virulence components, reduces its growth, and remains protected within a biofilm matrix.
dc.subjectStaphylococcus aurues
dc.titleThe Response of Staphylococcus aureus to Culture in a Low-Fluid-Shear Environment
dc.type.materialtext and Immunology University of Texas Medical Branch at Galveston and Immunology (Doctoral)


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