In FY 2013, we continued investigation of the staphylococcal peptide cytolysins, phenol-soluble modulins (PSMs). Current efforts focus on structure-function relationship studies of PSMs, antimicrobial activities of PSMs, and the PSM exporter, with the long-term goals to produce anti-PSM therapeutics for the treatment of staphylococcal infections. We have identified the PSM exporter and are currently setting up translational follow-up projects to find drugs interfering with PSM export. We also produced monoclonal antibodies targeting the SasX protein, previously identified to promote colonization and infection of a variety of epidemic MRSA strains in China. These will be tested in the future for a potential inhibition of colonization/infection.

Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
2013
Total Cost
$884,987
Indirect Cost
City
State
Country
Zip Code
Chen, Yan; Yeh, Anthony J; Cheung, Gordon Y C et al. (2015) Basis of virulence in a Panton-Valentine leukocidin-negative community-associated methicillin-resistant Staphylococcus aureus strain. J Infect Dis 211:472-80
Cheung, Gordon Y C; Villaruz, Amer E; Joo, Hwang-Soo et al. (2014) Genome-wide analysis of the regulatory function mediated by the small regulatory psm-mec RNA of methicillin-resistant Staphylococcus aureus. Int J Med Microbiol 304:637-44
Rudkin, Justine K; Laabei, Maisem; Edwards, Andrew M et al. (2014) Oxacillin alters the toxin expression profile of community-associated methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 58:1100-7
Sully, Erin K; Malachowa, Natalia; Elmore, Bradley O et al. (2014) Selective chemical inhibition of agr quorum sensing in Staphylococcus aureus promotes host defense with minimal impact on resistance. PLoS Pathog 10:e1004174
Berube, Bryan J; Sampedro, Georgia R; Otto, Michael et al. (2014) The psm? locus regulates production of Staphylococcus aureus alpha-toxin during infection. Infect Immun 82:3350-8
Uhlemann, Anne-Catrin; Otto, Michael; Lowy, Franklin D et al. (2014) Evolution of community- and healthcare-associated methicillin-resistant Staphylococcus aureus. Infect Genet Evol 21:563-74
Cheung, Gordon Y C; Kretschmer, Dorothee; Duong, Anthony C et al. (2014) Production of an attenuated phenol-soluble modulin variant unique to the MRSA clonal complex 30 increases severity of bloodstream infection. PLoS Pathog 10:e1004298
Otto, Michael (2014) Staphylococcus aureus toxins. Curr Opin Microbiol 17:32-7
Cheung, Gordon Y C; Kretschmer, Dorothee; Queck, Shu Y et al. (2014) Insight into structure-function relationship in phenol-soluble modulins using an alanine screen of the phenol-soluble modulin (PSM) *3 peptide. FASEB J 28:153-61
Otto, Michael (2014) Phenol-soluble modulins. Int J Med Microbiol 304:164-9

Showing the most recent 10 out of 37 publications