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

Abstract

dBiofilms 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.

New trends in peptide-based anti-biofilm strategies: a review of recent achievements and bioinformatic approaches

“…LL-37 is also capable of inhibiting initial biofilm attachment (by 58-62%), suggesting that peptides of this kind may be interacting with bacterial adhesins as part of their anti-biofilm mechanism (Dean et al 2011). Another study (de la Fuente-Nu´n˜ez et al 2012) also showed that the AMP 1037 directly inhibits biofilms by reducing swimming and swarming motilities, stimulating twitching motility, and suppressing the expression of a variety of genes involved in biofilm formation in P. aeruginosa (eg PA2204).…”

Type IV Pilin Proteins: Versatile Molecular Modules

“…The role of twitching motility in biofilm biology is complex, however, as stimuli that increase twitching motility during early development can reduce the extent of irreversible attachment, which is necessary for further stages to proceed. Studies of P. aeruginosa showed that stimulation of twitching through increased rhamnolipid synthesis, caused by the chelation of iron or treatment with small molecules, peptides, or complex natural products such as ginseng, decreased biofilm formation (118,158,356,412,417).…”

The effect of marT gene on biofilm production of Salmonella Typhimurium

“…These data prove that biofilm production is negatively regulated by the marT gene in S. Typhimurium. A total of 80% of all bacterial infections are caused by biofilm structures (de la Fuente-Núñez et al, 2012). Today, biofilms that are accepted as the predominant form of bacterial growth constitute the most complex examples of extracellular and intercellular organization.…”