Open AccessBeta-Lactamase Repressor BlaI Modulates Staphylococcus aureus Cathelicidin Antimicrobial Peptide Resistance and Virulence
Author(s) -
Morgan A. Pence,
Nina M. Haste,
Hiruy S. Meharena,
Joshua Olson,
Richard L. Gallo,
Victor Nizet,
Sascha A. Kristian
Publication year - 2015
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0136605
Subject(s) - cathelicidin , staphylococcus aureus , microbiology and biotechnology , antimicrobial , virulence , penicillin , biology , antibiotic resistance , innate immune system , repressor , virology , antimicrobial peptides , bacteria , immune system , antibiotics , immunology , gene , genetics , transcription factor
BlaI is a repressor of BlaZ, the beta-lactamase responsible for penicillin resistance in Staphylococcus aureus . Through screening a transposon library in S . aureus Newman for susceptibility to cathelicidin antimicrobial peptide, we discovered BlaI as a novel cathelicidin resistance factor. Additionally, through integrational mutagenesis in S . aureus Newman and MRSA Sanger 252 strains, we confirmed the role of BlaI in resistance to human and murine cathelidicin and showed that it contributes to virulence in human whole blood and murine infection models. We further demonstrated that BlaI could be a target for innate immune-based antimicrobial therapies; by removing BlaI through subinhibitory concentrations of 6-aminopenicillanic acid, we were able to sensitize S . aureus to LL-37 killing.
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