Staphylococci cause diseases via the production of toxic exomolecules including proteases, nucleases, toxins, etc. known collectively as virulence factors (VF). Recent work from this lab indicates that the expression of virulence factors in S. aureus is controlled by an autocrine regulatory system. The bacteria secrete into the medium a protein (termed RNAIII Activating Protein, or RAP) that upregulates the set of genes (accessory global regulon, agr) which controls virulence, thus leading to toxin synthesis. Previous work demonstrated that agr mutants of S. aureus have greatly reduced virulence in animal models. Preliminary data indicates that anti-RAP antibodies inhibit toxin synthesis in vitro, and in mice levels of anti-RAP antibodies correlate with resistance to S. aureus infection and vaccination with purified RAP attenuates S aureus infection. The overall goal of this project is to develop an anti-RAP vaccine to inhibit virulence factor synthesis to suppress staphylococcal infections. In Phase I RAP will be cloned using the N-terminal protein sequence, the cloned rRAP will be expressed and used to immunize rodents to demonstrate attenuation of S. aureus infection. This approach will have obvious synergy to conventional approaches.
Staphylococcus aureus is a major human pathogen. A new means to curtail this pathogen will have significant market opportunities.
