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Infection and Immunity, September 2008, p. 4176-4182, Vol. 76, No. 9
0019-9567/08/$08.00+0     doi:10.1128/IAI.00318-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Human Host Defense Peptide LL-37 Prevents Bacterial Biofilm Formation{triangledown} ,{dagger}

Joerg Overhage,1 Andrea Campisano,2 Manjeet Bains,1 Ellen C. W. Torfs,1 Bernd H. A. Rehm,2 and Robert E. W. Hancock1*

Centre for Microbial Diseases & Immunity Research, University of British Columbia, 2259 Lower Mall, Vancouver, British Columbia, Canada,1 Institute of Molecular Biosciences, Massey University, Private Bag 11222, Palmerston North, New Zealand2

Received 10 March 2008/ Returned for modification 22 April 2008/ Accepted 25 June 2008

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 defense 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 the very low and physiologically meaningful concentration of 0.5 µg/ml, far below that required to kill or inhibit growth (MIC = 64 µg/ml). LL-37 also affected 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 subinhibitory 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 affected biofilm formation by decreasing the attachment of bacterial cells, stimulating twitching motility, and influencing two major quorum sensing systems (Las and Rhl), leading to the downregulation of genes essential for biofilm development.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of British Columbia, No. 232 2259 Lower Mall, Lower Mall Research Station, Vancouver, British Columbia V6T 1Z4, Canada. Phone: (604) 822-2682. Fax: (604) 827-5566. E-mail: bob{at}cmdr.ubc.ca

{triangledown} Published ahead of print on 30 June 2008.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: A. J. Bäumler

Infection and Immunity, September 2008, p. 4176-4182, Vol. 76, No. 9
0019-9567/08/$08.00+0     doi:10.1128/IAI.00318-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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