title: Inhibition of bacterial biofilm formation and swarming motility by a small synthetic cationic peptide.
abstract: Biofilms cause up to 80% of infections and are difficult to treat due to their substantial multidrug resistance compared to their planktonic counterparts. Based on the observation that human peptide LL-37 is able to block biofilm formation at concentrations below its MIC, we screened for small peptides with antibiofilm activity and identified novel synthetic cationic peptide 1037 of only 9 amino acids in length. Peptide 1037 had very weak antimicrobial activity, but at 1/30th the MIC the peptide was able to effectively prevent biofilm formation (>50% reduction in cell biomass) by the Gram-negative pathogens Pseudomonas aeruginosa and Burkholderia cenocepacia and Gram-positive Listeria monocytogenes. Using a flow cell system and a widefield fluorescence microscope, 1037 was shown to significantly reduce biofilm formation and lead to cell death in biofilms. Microarray and follow-up studies showed that, in P. aeruginosa, 1037 directly inhibited biofilms by reducing swimming and swarming motilities, stimulating twitching motility, and suppressing the expression of a variety of genes involved in biofilm formation (e.g., PA2204). Comparison of microarray data from cells treated with peptides LL-37 and 1037 enabled the identification of 11 common P. aeruginosa genes that have a role in biofilm formation and are proposed to represent functional targets of these peptides. Peptide 1037 shows promise as a potential therapeutic agent against chronic, recurrent biofilm infections caused by a variety of bacteria.
authors.affiliation: Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
authors.forename: César
authors.initials: C
authors.lastname: de la Fuente-Núñez
authors.forename: Victoria
authors.initials: V
authors.lastname: Korolik
authors.forename: Manjeet
authors.initials: M
authors.lastname: Bains
authors.forename: Uyen
authors.initials: U
authors.lastname: Nguyen
authors.forename: Elena B M
authors.initials: EB
authors.lastname: Breidenstein
authors.forename: Shawn
authors.initials: S
authors.lastname: Horsman
authors.forename: Shawn
authors.initials: S
authors.lastname: Lewenza
authors.forename: Lori
authors.initials: L
authors.lastname: Burrows
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D018988:Bacterial Translocation / Q000187:drug effects; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D057508:Burkholderia cenocepacia / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D008089:Listeria monocytogenes / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D008856:Microscopy, Fluorescence; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides