Development of a Dominant Negative Competence-Stimulating Peptide (dnCSP) that Attenuates Streptococcus pneumoniae Infectivity in a Mouse Model of Acute Pneumonia

Bimal Koirala, Jingjun Lin, Gee W. Lau, Yftah Tal-Gan

Research output: Contribution to journalArticle

Abstract

Streptococcus pneumoniae (pneumococcus) is a prevalent human pathogen responsible for a variety of diseases, including pneumonia, bacteremia, sepsis, meningitis and otitis media, with a death toll of >22 000 a year in the United States alone. Pneumococcus uses the competence regulon and its associated signaling peptide, the competence stimulating peptide (CSP), to initiate its attack on the host and establish an infection. In this work, we set out to: 1) develop a pan-group quorum sensing inhibitor that could effectively interact with both the pneumococcus ComD1 and ComD2 receptors; and 2) evaluate the utility of dominant-negative CSPs (dnCSPs) in attenuating pneumococcus infectivity. Our results highlight the potential of inhibiting the competence regulon as a therapeutic approach to combat pneumococcus infections.

Original languageEnglish (US)
Pages (from-to)2380-2386
Number of pages7
JournalChemBioChem
Volume19
Issue number22
DOIs
StatePublished - Nov 16 2018

Keywords

  • Streptococcus pneumoniae
  • competence stimulating peptide
  • quorum sensing

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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