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Development of Streptococcus pneumoniae Pan‐Group Quorum‐Sensing Modulators
Author(s) -
Koirala Bimal,
TalGan Yftah
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201900365
Subject(s) - quorum sensing , streptococcus pneumoniae , virulence , microbiology and biotechnology , regulon , biology , pathogen , antibiotics , antibiotic resistance , computational biology , bacteria , bacterial protein , gene , genetics
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.