Characterization of an Autoinducing Peptide Signal Reveals Highly Efficacious Synthetic Inhibitors and Activators of Quorum Sensing and Biofilm Formation in .

Bacteria can use chemical signals to assess their local population density in a process called quorum sensing (QS). Many of these bacteria are common pathogens, including Gram-positive bacteria that utilize QS systems regulated by macrocyclic autoinducing peptide (AIP) signals. , an important foodborne pathogen, uses an system to regulate a variety of virulence factors and biofilm formation, yet little is known about the specific roles of in infection and its persistence in various environments. Herein, we report synthetic peptide tools that will enable the study of QS in . We identified a 6-mer AIP signal in supernatants and selected it as a scaffold around which a collection of non-native AIP mimics was designed and synthesized. These peptides were evaluated in cell-based reporter assays to generate structure-activity relationships for AIP-based agonism and antagonism in . We discovered synthetic agonists with increased potency relative to native AIP and a synthetic antagonist capable of reducing activity to basal levels. Notably, the latter peptide was able to reduce biofilm formation by over 90%, a first for a synthetic QS modulator in wild-type . The lead agonist and antagonist in were also capable of antagonizing signaling in the related pathogen , further extending their utility and suggesting different mechanisms of activation in these two pathogens. This study represents an important first step in the application of chemical methods to modulate QS and concomitant virulence outcomes in .