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Antimicrob Agents Chemother. 2015 Jul;59(7):3906-12. doi: 10.1128/AAC.00092-15. Epub 2015 Apr 20.

Antibiofilm peptides increase the susceptibility of carbapenemase-producing Klebsiella pneumoniae clinical isolates to β-lactam antibiotics.

Author information

1
Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Centro de Análises Proteômicas e Bioquímicas, Universidade Católica de Brasília, Brasília, Brazil.
2
Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
3
LACEN, Laboratório Central de Saúde Pública do Distrito Federal, Brasília, DF, Brazil.
4
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.
5
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.

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.

PMID:
25896694
PMCID:
PMC4468710
DOI:
10.1128/AAC.00092-15
[Indexed for MEDLINE]
Free PMC Article

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