Development of Streptococcus pneumoniae Pan-Group Quorum-Sensing Modulators.

ABSTRACT: The rapid increase in multidrug-resistant pathogens is a major health concern that could bring mankind back to the pre-antibiotic era. Streptococcus pneumoniae is a highly recombinogenic opportunistic pathogen that causes a variety of deadly diseases and rapidly develops resistance to current antibiotic treatments. S.?pneumoniae pathogenicity is dependent on a cell-density communication mechanism, or quorum sensing (QS), termed the competence regulon. In this work, we set out to design signal-based QS modulators capable of affecting the two specificity groups found in S.?pneumoniae. Through systematic analysis and rational design, we were able to construct peptide-based pan-group QS activators and inhibitors with activities in the nanomolar range. These novel analogues are privileged scaffolds for the development of anti-virulence therapeutics against S.?pneumoniae infections.

SUBMITTER: Koirala B 

PROVIDER: S-EPMC6952583 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature