Inhibition of virulence factor expression in Staphylococcus aureus by the Staphylococcus epidermidis agr pheromone and derivatives

The agr quorum-sensing system in Staphylococci controls the production of surface proteins and exoproteins, In the pathogenic species Staphylococcus aureus, these proteins include many virulence factors. The extracellular signal of the quorum-sensing system is a thiolactone-containing peptide pheromone, whose sequence varies among the different staphylococcal strains. We demonstrate that a synthetic Staphylococcus epidermidis pheromone is a competent inhibitor of the Staphylococcus aureus agr system. Derivatives of the pheromone, in which the N-terminus or the cyclic bond structure was changed, were synthesized and their biological activity was determined. The presence of a correct N-terminus and a thiolactone were absolute prerequisites for an agr-activating effect in S. epidermidis, whereas inhibition of the S, aureus agr system was less dependent on the original structure, Our results show that effective quorum-sensing blockers that suppress the expression of virulence factors in S, aureus can be designed based on the S, epidermidis pheromone. (C) 1999 Federation of European Biochemical Societies.