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Small molecule inhibition of Staphylococcus aureus virulence


Please use this identifier to cite or link to this item: http://hdl.handle.net/1928/13173

Small molecule inhibition of Staphylococcus aureus virulence

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dc.contributor.author Sully, Erin
dc.date.accessioned 2011-08-31T16:29:28Z
dc.date.available 2011-08-31T16:29:28Z
dc.date.issued 2011-08-31
dc.date.submitted July 2011
dc.identifier.uri http://hdl.handle.net/1928/13173
dc.description.abstract The 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.iso en_US en_US
dc.subject CA-MRSA en_US
dc.subject staphylococcus aureus en_US
dc.subject small molecule inhibitor en_US
dc.subject high-throughput screen en_US
dc.subject virulence en_US
dc.subject quorum sensing en_US
dc.subject.lcsh Staphylococcus aureus infections--Prevention.
dc.subject.lcsh Virulence (Microbiology)--Molecular aspects.
dc.title Small molecule inhibition of Staphylococcus aureus virulence en_US
dc.type Dissertation en_US
dc.description.degree Biomedical Sciences en_US
dc.description.level Doctoral en_US
dc.description.department University of New Mexico. Biomedical Sciences Graduate Program en_US
dc.description.advisor Gresham, Hattie
dc.description.committee-member Gresham, Hattie
dc.description.committee-member Hall, Pamela
dc.description.committee-member Mold, Carolyn
dc.description.committee-member Ozbun, Michelle

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