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dc.contributor.authorPeterson, Meghan Michal
dc.date.accessioned2010-06-28T22:27:47Z
dc.date.available2010-06-28T22:27:47Z
dc.date.issued2010-06-28T22:27:47Z
dc.date.submittedMay 2010
dc.identifier.urihttp://hdl.handle.net/1928/10900
dc.description.abstractStaphylococcus aureus is a colonizer of the human skin and mucosa that can cause minor to severe disease. Originally afflicting patients at the extremes of age or those with immunocompromising co-morbidities, S. aureus strains have emerged that cause invasive disease in otherwise healthy populations with no health-care associated risk factors. In addition, these community-acquired strains predominately contain antibiotic resistance genes, making them difficult to treat with conventional interventions. Invasive disease in S. aureus is partly regulated by a quorum sensing signaling system that relies on the secretion and signaling function of a bacterial peptide pheromone (AIP). S. aureus strains that lack this virulence regulator system still cause disease, but it is much less severe and is typified by a colonizing, rather than an invasive, phenotype. Therapeutics or host factors that inhibit virulence instead of viability can limit both invasive disease as well as the development of resistance. During infection, the inflammatory process causes serum to extravasate into the affected tissue site. Serum has been shown to inhibit virulence signaling in S. aureus, though the mechanism is unknown. This dissertation identifies apolipoprotein B (apoB), the major protein component of very low and low density lipoproteins, as a potent inhibitor of virulence signaling in S. aureus by binding the bacterial signaling pheromone AIP. Though binding of host lipoproteins to bacterial products has been described in Gram-negative infections, this is the first demonstration of a lipoprotein component having protective effects in a Gram-positive infection. This work further describes the inhibitory action of apoB on virulence signaling and subsequent invasive infection in multiple S. aureus strains and identifies the globular amino terminal domain of apoB as the AIP binding site. These findings have important implications for understanding the host-pathogen interaction and for developing therapeutics that can be effective without causing bacterial resistance.en_US
dc.description.sponsorshipNational Institutes of Health Grant AI-064926, Department of Veterans Affairs, University of New Mexico School of Medicine Research Allocation Committee Granten_US
dc.language.isoen_USen_US
dc.subjectMRSAen_US
dc.subjectS. aureusen_US
dc.subjecthost defenseen_US
dc.subjectserum lipoproteinsen_US
dc.subjectapolipoprotein Ben_US
dc.subjectinfectionen_US
dc.subject.lcshStaphylococcus aureus infections--Chemotherapy.
dc.subject.lcshApolipoprotein B
dc.titleApolipoprotein B-mediated control of Staphylococcus aureus virulenceen_US
dc.typeDissertationen_US
dc.description.degreeBiomedical Sciencesen_US
dc.description.levelDoctoralen_US
dc.description.departmentUniversity of New Mexico. Biomedical Sciences Graduate Programen_US
dc.description.advisorGresham, Hattie
dc.description.committee-memberMold, Carolyn
dc.description.committee-memberChackerian, Bryce
dc.description.committee-memberTimmins, Graham
dc.description.committee-memberHall, Pamela


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