Synthetic cyclic peptide modulators of the AgrC quorum sensing system of S. epidermidis. Synthetic agonists and antagonist of AgrC-I are described. Compounds capable of either pan-group or group-selective AgrC receptor inhibition in S. epidermidis were identified. Additionally, compounds that are species selective, and could be applied to selectively modulate either S. epidermidis or S. aureus AgrC receptors were identified. An AgrC-I agonist was found which strongly inhibits S. epidermidis biofilm growth, with a higher potency and efficacy than that of native AIP-I. Methods of modulating virulence in S. epidermidis and related Staphylococcus by contacting a bacterium or a bacterial environment, such as a biofilm, with a modulator of the disclosure are provided. Methods are provided for treating infections of S. epidermidis and related Staphylococcus by administering a therapeutically effective amount of one or more compounds herein to an individual in need thereof.
