AUTOCRINE REGULATION OF TOXIN SYNTHESIS BY STAPHYLOCOCCUS-AUREUS

Staphylococcus aureus is a major human pathogen causing diseases which range from minor skin infection to endocarditis and toxic shock syndr ome. The pathogenesis of S. aureus is due primarily to the production of toxic exoproteins, whose synthesis is controlled by a global regula tory system, agr. We show here that agr is autoinduced by a proteinace ous factor produced and secreted by the bacteria and that it is inhibi ted by a peptide produced by an exoprotein-deficient S. aureus mutant strain. The inhibitor, RIP, competes with the activator, RAP, and may be a mutational derivative. Our results suggest two possible approache s, independent of antibiotics, to the control of S. aureus infections. RIP may prove useful as a direct inhibitor of virulence and RAP as a vaccine against the expression of agr-induced virulence factors; eithe r could interfere with the ability of the bacteria to establish and ma intain an infection.