Repression of Virulence in Staphylococcus aureus by 2-Aminothiol-Mediated Quorum Quenching

We present a novel strategy for the inhibition of quorum sensing in Staphylococcus bacteria. Previous work has focused on the development of peptides that can compete with native autoinducing peptides (AIPs), to antagonize the receptor histidine kinase responsible for activation of quorum sensing and thereby repress the expression of virulence genes. Here we report simple analogues of cysteine that can eliminate the native AIPs extracellularly, before they activate their receptor, and validate that this alternative strategy can also be applied to turn off quorum sensing in different Staphylococcus aureus reporter strain assays. Further, we show that two selected compounds can reduce skin infection caused by MRSA in a murine model. This work provides impetus for the development of simple small molecules for the topical treatment of staphylococcal skin infections. We anticipate that further studies, including delivery strategies, will help illuminate this potential.