title: Beta-Lactamase Repressor BlaI Modulates Staphylococcus aureus Cathelicidin Antimicrobial Peptide Resistance and Virulence.
abstract: 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.
authors: Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA, United States of America; Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA, United States of America.
authors: Morgan A
authors: MA
authors: Pence
authors: Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA, United States of America; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, United States of America.
authors: Nina M
authors: NM
authors: Haste
authors: Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA, United States of America.
authors: Hiruy S
authors: HS
authors: Meharena
authors: Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA, United States of America.
authors: Joshua
authors: J
authors: Olson
authors: Department of Dermatology, School of Medicine, University of California San Diego, La Jolla, CA, United States of America; VA San Diego Healthcare System, San Diego, CA, United States of America.
authors: Richard L
authors: RL
authors: Gallo
authors: Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA, United States of America; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, United States of America.
authors: Victor
authors: V
authors: Nizet
authors: Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA, United States of America.
authors: Sascha A
authors: SA
authors: Kristian
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage*; D004251:DNA Transposable Elements / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006801:Humans; D051379:Mice; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D010403:Penicillin Resistance / Q000235:genetics; D013203:Staphylococcal Infections / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics* / Q000472:pathogenicity; D001618:beta-Lactamases / Q000235:genetics*; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D004251:DNA Transposable Elements; D010397:Penicillanic Acid; D001618:beta-Lactamases; C004408:aminopenicillanic acid; D054804:Cathelicidins