Peptide analogues of the Streptococcus mutans competence stimulating peptide (CSP) as inhibitors of quorum sensing

Streptococcus mutans is considered a major causative agent of dental caries. S. mutans utilizes quorum sensing systems to regulate the expression of several virulence factors, including genetic competence, acid tolerance, and biofilm formation. One of the S. mutans quorum sensing systems comprises a competence stimulating peptide (CSP) and a two-component signal transduction system. In this study, 22 CSP analogues were synthesized based on the mature CSP sequence and assayed for their ability to inhibit genetic competence, growth at pH 5.5 and biofilm formation in S. mutans. Analogue H1, synthesized by deleting the alanine residue at position 18 from the mature CSP sequence, was able to competitively inhibit genetic competence. Analogue E2, synthesized by substituting the arginine residue at position 13 with alanine, was able to impair biofilm formation. We demonstrated that by altering the native amino acid sequence of the S. mutans CSP, effective quorum sensing inhibitors can be created.