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dc.contributor.authorSully, Erin
dc.date.accessioned2011-08-31T16:29:28Z
dc.date.available2011-08-31T16:29:28Z
dc.date.issued2011-08-31
dc.date.submittedJuly 2011
dc.identifier.urihttp://hdl.handle.net/1928/13173
dc.description.abstractThe increasing emergence of antibiotic resistant Staphylococcus aureus infections, particularly those caused by a single clone of methicillin resistant S. aureus (USA300 MRSA), coupled with the slowing of antibiotic discovery makes research into novel therapies a priority (Lowy, 2007). One strategy evolving is the development of drugs that target bacterial virulence factors as opposed to growth (Cegelski et al., 2008). Due to the lack of selective pressure, bacterial resistance to the drugs would be minimized while the infection, attenuated by the inhibition of virulence factor production, could be cleared by the innate immune factors of the host. Virulence factors identified to date as essential for invasive USA 300 MRSA infection are globally regulated in part by a quorum sensing operon, agr (George and Muir, 2007; Novick and Geisinger, 2008; Yarwood and Schlievert, 2003). Host factors like apolipoprotein B provide defense by antagonizing agr signaling which demonstrates that host defense against an invasive infection could be accomplished by blocking agr signaling (Peterson et al., 2008). Therefore, we hypothesized that screening small molecule inhibitors for inhibition of agr signaling could contribute to drug discovery by providing optimal host defense against quorum sensing dependent S. aureus infections. Our work focuses on two small molecule inhibitors, CID# 2333 and CID# 3243271, identified in a screen of over 20,000 compounds for antagonism of agr signaling. These compounds demonstrate virulence factor inhibition in vitro and in an in vivo model of community associated -MRSA dermonecrotic infection.en_US
dc.language.isoen_USen_US
dc.subjectCA-MRSAen_US
dc.subjectstaphylococcus aureusen_US
dc.subjectsmall molecule inhibitoren_US
dc.subjecthigh-throughput screenen_US
dc.subjectvirulenceen_US
dc.subjectquorum sensingen_US
dc.subject.lcshStaphylococcus aureus infections--Prevention.
dc.subject.lcshVirulence (Microbiology)--Molecular aspects.
dc.titleSmall molecule inhibition 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-memberGresham, Hattie
dc.description.committee-memberHall, Pamela
dc.description.committee-memberMold, Carolyn
dc.description.committee-memberOzbun, Michelle


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