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Development of a Dominant Negative Competence‐Stimulating Peptide (dnCSP) that Attenuates Streptococcus pneumoniae Infectivity in a Mouse Model of Acute Pneumonia
Author(s) -
Koirala Bimal,
Lin Jingjun,
Lau Gee W.,
TalGan Yftah
Publication year - 2018
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.201800505
Subject(s) - streptococcus pneumoniae , regulon , microbiology and biotechnology , infectivity , pneumonia , immunology , pathogen , meningitis , otitis , biology , medicine , gene , bacterial protein , antibiotics , virus , biochemistry , genetics , psychiatry
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.

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