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Applied and Environmental Microbiology, November 2008, p. 6639-6648, Vol. 74, No. 21
0099-2240/08/$08.00+0     doi:10.1128/AEM.01262-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Brominated Furanones Inhibit Biofilm Formation by Salmonella enterica Serovar Typhimurium {triangledown}

Joost C. A. Janssens,1,2 Hans Steenackers,1,2 Stijn Robijns,1 Edith Gellens,1 Jeremy Levin,2 Hui Zhao,1 Kim Hermans,1 David De Coster,1 Tine L. Verhoeven,1 Kathleen Marchal,1 Jos Vanderleyden,1 Dirk E. De Vos,2 and Sigrid C. J. De Keersmaecker1*

Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Kasteelpark Arenberg 20, B-3001 Leuven, Belgium,1 Centre for Surface Chemistry and Catalysis, Katholieke Universiteit Leuven, Kasteelpark Arenberg 23, B-3001 Leuven, Belgium2

Received 6 June 2008/ Accepted 7 September 2008

Salmonella enterica serovar Typhimurium is a main cause of bacterial food-borne diseases. As Salmonella can form biofilms in which it is better protected against antimicrobial agents on a wide diversity of surfaces, it is of interest to explore ways to inhibit biofilm formation. Brominated furanones, originally extracted from the marine alga Delisea pulchra, are known to interfere with biofilm formation in several pathogens. In this study, we have synthesized a small focused library of brominated furanones and tested their activity against S. enterica serovar Typhimurium biofilm formation. We show that several furanones inhibit Salmonella biofilm formation at non-growth-inhibiting concentrations. The most interesting compounds are (Z)-4-bromo-5-(bromomethylene)-3-alkyl-2(5H)-furanones with chain lengths of two to six carbon atoms. A microarray study was performed to analyze the gene expression profiles of Salmonella in the presence of (Z)-4-bromo-5-(bromomethylene)-3-ethyl-2(5H)-furanone. The induced genes include genes that are involved in metabolism, stress response, and drug sensitivity. Most of the repressed genes are involved in metabolism, the type III secretion system, and flagellar biosynthesis. Follow-up experiments confirmed that this furanone interferes with the synthesis of flagella by Salmonella. No evidence was found that furanones act on the currently known quorum-sensing systems in Salmonella. Interestingly, pretreatment with furanones rendered Salmonella biofilms more susceptible to antibiotic treatment. Conclusively, this work demonstrates that particular brominated furanones have potential in the prevention of biofilm formation by Salmonella serovar Typhimurium.

* Corresponding author. Mailing address: Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Kasteelpark Arenberg 20, B-3001 Leuven, Belgium. Phone: 32-16321631. Fax: 32-16321966. E-mail: Sigrid.DeKeersmaecker{at}biw.kuleuven.be

{triangledown} Published ahead of print on 12 September 2008.

Applied and Environmental Microbiology, November 2008, p. 6639-6648, Vol. 74, No. 21
0099-2240/08/$08.00+0     doi:10.1128/AEM.01262-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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