Inhibition of bacterial biofilm formation and swarming motility by a small synthetic cationic peptide

César De La Fuente-Núñez, Victoria Korolik, Manjeet Bains, Uyen Nguyen, Elena B.M. Breidenstein, Shawn Horsman, Shawn Lewenza, Lori Burrows, Robert E.W. Hancock

Research output: Contribution to journalJournal Articlepeer-review

361 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2696-2704
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume56
Issue number5
DOIs
Publication statusPublished - May 2012

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