Attenuating the Streptococcus pneumoniae Competence Regulon Using Urea-Bridged Cyclic Dominant-Negative Competence-Stimulating Peptide Analogs.

ABSTRACT: Streptococcus pneumoniae (pneumococcus) is a prevalent human pathogen that utilizes the competence regulon quorum sensing circuitry to acquire antibiotic resistance and initiate its attack on the human host. Therefore, targeting the competence regulon can be applied as an anti-infective approach with minimal pressure for resistance development. Herein, we report the construction of a library of urea-bridged cyclic dominant-negative competence-stimulating peptide (dnCSP) derivatives and their evaluation as competitive inhibitors of the competence regulon. Our results reveal the first pneumococcus dual-action CSPs that inhibit the group 1 pneumococcus competence regulon while activating the group 2 pneumococcus competence regulon. Structural analysis indicates that the urea-bridge cyc

SUBMITTER: Lella M 

PROVIDER: S-EPMC9106926 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature