Biological Evaluation of Native Streptococcal Competence Stimulating Peptides Reveal Potential Crosstalk Between and and a New Scaffold for the Development of Quorum Sensing Modulators.

, an opportunistic human pathogen, acquires genes from its neighboring species of the mitis group of streptococci that confer antibiotic resistances and allow it to produce diverse virulence factors. Most species of the mitis group are naturally competent, and they utilize the competence stimulating peptide (CSP) and the CSP-dependent competence regulon, a conserved quorum sensing (QS) circuit, to regulate their competence behavior. The dependence of the mitis group on this communication pathway makes QS a potential target to control their behavior. In this work, we sought to evaluate the impact of native pheromones of the adjacent species of to modulate the activity of the competence regulon. Our results revealed the potential role of as a modulator of QS in . Most importantly, our analysis also revealed that by using the native pheromone of as a template, highly potent pan-group agonists and antagonists of the pneumococcal competence regulon could be developed. The newly developed QS modulators may have therapeutic utility in treating pneumococcus infections.