Quorum sensing (QS), a cell-density based mechanism utilized by bacteria to regulate group-related phenotypes, has attracted considerable attention as a means to attenuate bacterial pathogenesis. Many Gram-positive bacterial species utilize peptide pheromones to induce QS responses and initiate pathogenic phenotypes, such as competence, biofilm formation and virulence factor production. We investigate the molecular mechanisms that drive signal-receptor binding while interrogating the role of QS in the competition between bacterial species. To this end, we develop peptide-based QS modulators with distinct activity profiles (selective vs. pan-species modulators; inhibitors vs. activators) to test temporal control of QS modulation in both single-species and mixed cultures. This presentation will be focused on our recent progress and on-going studies of the competence stimulation peptide (CSP)-based and gelatinase biosynthesis activating pheromone (GBAP)-based QS circuits in Streptococcus pneumoniae and Enterococcus faecalis, respectively.^1-6

References

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(2)   Koirala, B.; Hillman, R. A.; Tiwold, E. K.; Bertucci, M. A.; Tal-Gan, Y. Beilstein J Org Chem 2018, 14, 1769.

(3)   Yang, Y.; Cornilescu, G.; Tal-Gan, Y. Biochemistry 2018, 57, 5359.

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(6)   McBrayer, D. N.; Cameron, C. D.; Gantman, B. K.; Tal-Gan, Y. ACS Chem Biol 2018, 13, 2673.