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Book of Abstracts: Albany 2007

category image Albany 2007
Conversation 15
June 19-23 2007

Regulation of Virulence and Antibiotic Resistance in Pathogens

Staphylococcus aureus is a human pathogen responsible for most wound and hospital acquired infections. The extensive use of antibiotics to treat S. aureus infections has led to the emergence of high-level resistances in various strains. Virulence suppression provides an alternative strategy to effectively reduce pathogenic potential without asserting selective pressure for developing resistances. A recent breakthrough in my laboratory has identified the MgrA protein as a key virulence regulator in S. aureus. This protein belongs to the MarR family of transcriptional regulators that controls antibiotic resistance and virulence in various bacteria. We demonstrated that the mgrA knockout strain shows a 10,000-fold reduction of virulence in a murine abscess model. Subsequently, we discovered that oxidative stress leads to dissociation of MgrA from its promoter DNA (1). This discovery is significant in that the host immune response to S. aureus infection is to produce reactive oxygen and nitrogen species to counter the pathogen. The microorganism uses MgrA to sense the oxidative stress generated by the host and regulates a global defensive responses.

I will present the mechanism of MgrA and its regulation pathways as well as regulation roles of its close homologous in S. aureus. Preliminary results on developing small molecules that modulate functions of MgrA in order to suppress the virulence of S. aureus will be presented. Lastly, functions and mechanisms of other MarR family regulators in different pathogens will be discussed.

References and Footnotes
  1. Chen, P., Bae, T., Williams, W. A., Duguid, E. M., Rice, P. A., Schneewind, O., and He, C. Nature Chem Biol 2, 591-595 (2006).

Chuan He

Department of Chemistry
University of Chicago
5735 S. Ellis Avenue
Chicago, IL 60637, USA

Phone: 01-773-702-5061
Fax: 01-773-702-0805
Email: chuanhe@uchicago.edu