Inhibition of Bacterial Biofilm Formation and Swarming Motility by a Small Synthetic Cationic Peptide

TLDR

Biofilms account for up to 80 % of infections and are difficult to treat because they exhibit substantial multidrug resistance compared to planktonic bacteria. The study sought to discover small synthetic cationic peptides that inhibit biofilm formation, leading to the identification of peptide 1037, a 9‑amino‑acid construct. The authors screened LL‑37‑inspired peptides and selected peptide 1037, which was then tested for antibiofilm activity. Peptide 1037, with weak antimicrobial activity, prevented biofilm formation by >50 % at 1/30 MIC against *Pseudomonas aeruginosa*, *Burkholderia cenocepacia*, and *Listeria monocytogenes*, reduced biofilm biomass and induced cell death in flow‑cell assays, inhibited swimming and swarming motilities, stimulated twitching, down‑regulated biofilm‑related genes, shared 11 target genes with LL‑37, and thus shows promise as a therapeutic agent against chronic biofilm infections.

Abstract

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.