title: Antibiofilm peptides increase the susceptibility of carbapenemase-producing Klebsiella pneumoniae clinical isolates to β-lactam antibiotics.
abstract: Multidrug-resistant carbapenemase-producing Klebsiella pneumoniae (KpC) strains are becoming a common cause of infections in health care centers. Furthermore, Klebsiella can develop multicellular biofilms, which lead to elevated adaptive antibiotic resistance. Here, we describe the antimicrobial and antibiofilm activities of synthetic peptides DJK-5, DJK-6, and 1018 against five KpC isolates. Using static microplate assays, it was observed that the concentration required to prevent biofilm formation by these clinical isolates was below the MIC for planktonic cells. More-sophisticated flow cell experiments confirmed the antibiofilm activity of the peptides against 2-day-old biofilms of different KpC isolates, and in some cases, the peptides induced significant biofilm cell death. Clinically relevant combinations of DJK-6 and β-lactam antibiotics, including the carbapenem meropenem, also prevented planktonic growth and biofilm formation of KpC strain1825971. Interestingly, peptide DJK-6 was able to enhance, at least 16-fold, the ability of meropenem to eradicate preformed biofilms formed by this strain. Using peptide DJK-6 to potentiate the activity of β-lactams, including meropenem, represents a promising strategy to treat infections caused by KpC isolates.
authors.affiliation: Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Centro de Análises Proteômicas e Bioquímicas, Universidade Católica de Brasília, Brasília, Brazil.
authors.forename: Suzana Meira
authors.initials: SM
authors.lastname: Ribeiro
authors.affiliation: Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: César
authors.initials: C
authors.lastname: de la Fuente-Núñez
authors.affiliation: Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Beverlie
authors.initials: B
authors.lastname: Baquir
authors.affiliation: LACEN, Laboratório Central de Saúde Pública do Distrito Federal, Brasília, DF, Brazil.
authors.forename: Célio
authors.initials: C
authors.lastname: Faria-Junior
authors.affiliation: Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Centro de Análises Proteômicas e Bioquímicas, Universidade Católica de Brasília, Brasília, Brazil S-Inova, Pos-Graduação em Biotecnologia, Universidade Catolica Dom Bosco, Campo Grande, MS, Brazil ocfranco@gmail.com bob@hancocklab.com.
authors.forename: Octávio L
authors.initials: OL
authors.lastname: Franco
authors.affiliation: Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada ocfranco@gmail.com bob@hancocklab.com.
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018441:Biofilms / Q000187:drug effects*; D003470:Culture Media; D024881:Drug Resistance, Bacterial; D004357:Drug Synergism; D006801:Humans; D007710:Klebsiella Infections / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003470:Culture Media; D010455:Peptides; D047090:beta-Lactams; D001618:beta-Lactamases; C063912:carbapenemase