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Chembiochem. 2011 Dec 16;12(18):2759-66. doi: 10.1002/cbic.201100500. Epub 2011 Nov 2.

Palmitoyl-DL-carnitine is a multitarget inhibitor of Pseudomonas aeruginosa biofilm development.

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1
Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street W. Hamilton, ON L8S4K1, Canada.

Abstract

Bacteria growing in biofilms are often in metabolic and physiological states that do not respond well to antibiotics, and thus, are major contributors to chronic diseases. Biofilm inhibitors, therefore, have the potential to be used alone or as adjuvants to conventional antibiotic therapies. Here, we screened a chemically diverse collection of protein kinase inhibitors for molecules that perturb biofilm development. Among the inhibitory molecules identified, palmitoyl-DL-carnitine (pDLC) impaired Pseudomonas aeruginosa and Escherichia coli biofilm formation in a dose-dependent manner. The pDLC affected multiple pathways implicated in P. aeruginosa biofilm development; it stimulated motility, inhibited activity of the Las quorum sensing system, and overrode the biofilm-promoting effects of subminimal inhibitory concentrations of aminoglycosides and high levels of the second messenger, cyclic-di-GMP. Palmitic acid, but not carnitine, inhibited biofilm formation but did not stimulate motility, suggesting that pDLC works through unique mechanisms. The ability to target multiple pathways involved in biofilm formation is desirable in an inhibitor, which makes pDLC an interesting lead for antibiofilm therapies.

PMID:
22045628
DOI:
10.1002/cbic.201100500
[Indexed for MEDLINE]

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