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

Abstract

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.