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Infect. Immun. doi:10.1128/IAI.00318-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The human host defence peptide LL-37 prevents bacterial biofilm formation

Centre for Microbial Diseases & Immunity Research, University of British Columbia, 2259 Lower Mall, Vancouver BC, Canada; Institute of Molecular Biosciences, Massey University, Private Bag 11222, Palmerston North, New Zealand

^* To whom correspondence should be addressed. Email: bob{at}cmdr.ubc.ca.

	Abstract

The ability to form biofilms is a critical factor in chronic infections by Pseudomonas aeruginosa and has made this bacterium a model organism with respect to biofilm formation. This study describes a new, previously unrecognized role for the human cationic host defence peptide LL-37. In addition to its key role in modulating the innate immune response and weak antimicrobial activity, LL-37 potently inhibited the formation of bacterial biofilms in vitro. This occurred at very low and physiologically meaningful concentrations of 0.5 µg/ml, far below those required to kill or inhibit growth (MIC = 64 µg/ml). LL-37 also impacted on existing, pregrown P. aeruginosa biofilms. Similar results were obtained using the bovine neutrophil peptide indolicidin, but no inhibitory effect on biofilm formation was detected using sub-inhibitory concentrations of the mouse peptide CRAMP, which shares 67% identity with LL-37, polymyxin B, or the bovine bactenecin homolog Bac2A. Using microarrays and follow up studies we were able to demonstrate that LL-37 impacted on biofilm formation by decreasing attachment of bacterial cells, stimulating twitching motility and influencing two major quorum sensing systems (Las and Rhl), leading to the down-regulation of genes essential for biofilm development.