In FY 2010, we focused on continued investigation of the staphylococcal peptide cytolysins, phenol-soluble modulins (PSMs). In collaboration with Dr. Andreas Peschels group from the University of Tubingen, Germany, we discovered that the pro-inflammatory effects of PSMs on neutrophils are mediated by binding to the FPR2/ALX receptor. In contrast, cytolytic activities of PSMs are independent of that receptor. Furthermore, we found that several protein synthesis-inhibiting antibiotics, such as tetracycline and clindamycin, trigger increased production of PSMs and of the Agr virulence regulator, which controls PSM production. Current efforts focus on structure-function relationship studies of PSMs and the identification of the PSM exporter, with the long-term goals to produce anti-PSM therapeutics for the treatment of staphylococcal infections. In further work, we continued our efforts to elucidate the basis of virulence in community-associated MRSA strains. In particular, we are investigating the contribution of differential gene expression and production of major toxins to CA-MRSA virulence. These studies are performed in close collaboration with Dr. DeLeos group at RML, Dr. Diep at UCSF, and Dr. Li at Fudan University.

Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2010
Total Cost
$1,211,186
Indirect Cost
City
State
Country
Zip Code
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