A broad-spectrum antibiofilm peptide enhances antibiotic action against bacterial biofilms

Biofilm-related infections account for at least 65% of all human infections, but there are no available antimicrobials that specifically target biofilms. Their elimination by available treatments is inefficient since biofilm cells are between 10- and 1,000-fold more resistant to conventional antibio...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2014-09, Vol.58 (9), p.5363-5371
Main Authors: Reffuveille, Fany, de la Fuente-Núñez, César, Mansour, Sarah, Hancock, Robert E W
Format: Article
Language:English
Subjects:
Acinetobacter baumannii
Anti-Bacterial Agents
Anti-Bacterial Agents - pharmacology
Bacteria
Bacteria - drug effects
Bacteriology
Biofilms
Biofilms - drug effects
Drug Resistance, Multiple, Bacterial - drug effects
Enterobacter
Enterococcus faecium
Escherichia coli
Experimental Therapeutics
Klebsiella pneumoniae
Life Sciences
Microbial Sensitivity Tests - methods
Microbiology and Parasitology
Peptides
Peptides - pharmacology
Pseudomonas aeruginosa
Salmonella enterica
Staphylococcus aureus
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Summary:Biofilm-related infections account for at least 65% of all human infections, but there are no available antimicrobials that specifically target biofilms. Their elimination by available treatments is inefficient since biofilm cells are between 10- and 1,000-fold more resistant to conventional antibiotics than planktonic cells. Here we describe the synergistic interactions, with different classes of antibiotics, of a recently characterized antibiofilm peptide, 1018, to potently prevent and eradicate bacterial biofilms formed by multidrug-resistant ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens. Combinations of peptide 1018 and the antibiotic ceftazidime, ciprofloxacin, imipenem, or tobramycin were synergistic in 50% of assessments and decreased by 2- to 64-fold the concentration of antibiotic required to treat biofilms formed by Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, Salmonella enterica, and methicillin-resistant Staphylococcus aureus. Furthermore, in flow cell biofilm studies, combinations of low, subinhibitory levels of the peptide (0.8 μg/ml) and ciprofloxacin (40 ng/ml) decreased dispersal and triggered cell death in mature P. aeruginosa biofilms. In addition, short-term treatments with the peptide in combination with ciprofloxacin prevented biofilm formation and reduced P. aeruginosa PA14 preexisting biofilms. PCR studies indicated that the peptide suppressed the expression of various antibiotic targets in biofilm cells. Thus, treatment with the peptide represents a novel strategy to potentiate antibiotic activity against biofilms formed by multidrug-resistant pathogens.
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.03163-14