title: Brominated furanones inhibit biofilm formation by Salmonella enterica serovar Typhimurium.
abstract: 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.
authors.affiliation: Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Joost C A
authors.initials: JC
authors.lastname: Janssens
authors.forename: Hans
authors.initials: H
authors.lastname: Steenackers
authors.forename: Stijn
authors.initials: S
authors.lastname: Robijns
authors.forename: Edith
authors.initials: E
authors.lastname: Gellens
authors.forename: Jeremy
authors.initials: J
authors.lastname: Levin
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Kim
authors.initials: K
authors.lastname: Hermans
authors.forename: David
authors.initials: D
authors.lastname: De Coster
authors.forename: Tine L
authors.initials: TL
authors.lastname: Verhoeven
authors.forename: Kathleen
authors.initials: K
authors.lastname: Marchal
authors.forename: Jos
authors.initials: J
authors.lastname: Vanderleyden
authors.forename: Dirk E
authors.initials: DE
authors.lastname: De Vos
authors.forename: Sigrid C J
authors.initials: SC
authors.lastname: De Keersmaecker
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D005407:Flagella / Q000187:drug effects; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D015394:Molecular Structure; D020411:Oligonucleotide Array Sequence Analysis; D012486:Salmonella typhimurium / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D005663:Furans
references.citation: Nat Rev Microbiol. 2007 Jan;5(1):48-56
references.pmid: 17143318
references.citation: J Biol Chem. 1989 Dec 25;264(36):21670-6
references.pmid: 2600086
references.citation: Oral Microbiol Immunol. 2007 Oct;22(5):340-6
references.pmid: 17803632
references.citation: Appl Environ Microbiol. 2004 Aug;70(8):4941-9
references.pmid: 15294834
references.citation: Science. 1998 Apr 10;280(5361):295-8
references.pmid: 9535661
references.citation: Nat Rev Microbiol. 2008 Jun;6(6):455-65
references.pmid: 18483484
references.citation: Biomaterials. 2004 Sep;25(20):5023-30
references.pmid: 15109864
references.citation: Microbiology (Reading). 1999 Feb;145 ( Pt 2):283-291
references.pmid: 10075410
references.citation: Can J Vet Res. 2002 Apr;66(2):86-92
references.pmid: 11989739
references.citation: Nature. 2002 Jan 31;415(6871):545-9
references.pmid: 11823863
references.citation: J Infect Dis. 2005 Jun 1;191(11):1881-8
references.pmid: 15871122
references.citation: Microbiology (Reading). 2001 Sep;147(Pt 9):2517-2528
references.pmid: 11535791
references.citation: J Biol Chem. 2005 May 20;280(20):19563-8
references.pmid: 15790567
references.citation: Lett Appl Microbiol. 2002;34(4):293-9
references.pmid: 11940163
references.citation: J Bacteriol. 2004 Feb;186(3):692-8
references.pmid: 14729694
references.citation: Biotechnol Bioeng. 2004 Dec 5;88(5):630-42
references.pmid: 15470704
references.citation: FEMS Microbiol Lett. 2001 Nov 27;205(1):131-8
references.pmid: 11728727
references.citation: Prog Mol Subcell Biol. 2006;42:55-86
references.pmid: 16805438
references.citation: Annu Rev Genet. 2001;35:439-68
references.pmid: 11700290
references.citation: EMBO Rep. 2007 Jul;8(7):616-21
references.pmid: 17603533
references.citation: Appl Environ Microbiol. 2007 Jan;73(2):535-44
references.pmid: 17085703
references.citation: J Bacteriol. 1994 Jan;176(2):269-75
references.pmid: 8288518
references.citation: Biol Proced Online. 2003;5:189-196
references.pmid: 14615815
references.citation: J Clin Invest. 2003 Nov;112(9):1300-7
references.pmid: 14597754
references.citation: Mol Microbiol. 2004 May;52(4):933-45
references.pmid: 15130116
references.citation: Mol Microbiol. 2004 Apr;52(1):169-87
references.pmid: 15049819
references.citation: Trends Microbiol. 2005 Jan;13(1):27-33
references.pmid: 15639629
references.citation: Mol Cell. 2004 Sep 10;15(5):677-87
references.pmid: 15350213
references.citation: Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1639-44
references.pmid: 9990077
references.citation: Mol Microbiol. 2003 Nov;50(4):1411-27
references.pmid: 14622426
references.citation: Infect Immun. 2002 May;70(5):2640-9
references.pmid: 11953406
references.citation: Environ Microbiol. 2001 Nov;3(11):731-6
references.pmid: 11846763
references.citation: Arch Microbiol. 1977 Feb 4;112(1):73-9
references.pmid: 843170
references.citation: Nat Rev Microbiol. 2004 Feb;2(2):95-108
references.pmid: 15040259
references.citation: FEMS Microbiol Rev. 2004 Jun;28(3):261-89
references.pmid: 15449604
references.citation: Annu Rev Cell Dev Biol. 2005;21:319-46
references.pmid: 16212498
references.citation: J Antimicrob Chemother. 2001 Jul;48 Suppl 1:5-16
references.pmid: 11420333
references.citation: J Bacteriol. 2003 Feb;185(4):1357-66
references.pmid: 12562806
references.citation: Nature. 1981 May 21;291(5812):238-9
references.pmid: 7015147
references.citation: EMBO J. 2003 Aug 1;22(15):3803-15
references.pmid: 12881415
references.citation: Appl Environ Microbiol. 2006 Sep;72(9):6419-23
references.pmid: 16957276
references.citation: BMC Microbiol. 2004 Jul 02;4:25
references.pmid: 15233843
references.citation: J Bacteriol. 2007 Jul;189(13):4587-96
references.pmid: 17483226
references.citation: FEMS Microbiol Lett. 2007 Feb;267(2):200-6
references.pmid: 17156099
references.citation: Microbiology (Reading). 2002 Apr;148(Pt 4):1119-1127
references.pmid: 11932456
references.citation: J Bacteriol. 1996 Nov;178(22):6618-22
references.pmid: 8932319
references.citation: Mol Microbiol. 1996 Oct;22(2):367-78
references.pmid: 8930920
references.citation: Microbiology (Reading). 2006 Nov;152(Pt 11):3411-3424
references.pmid: 17074910
references.citation: J Bacteriol. 1998 Mar;180(5):1185-93
references.pmid: 9495757
references.citation: Microbiology (Reading). 2002 Jan;148(Pt 1):87-102
references.pmid: 11782502
references.citation: J Bacteriol. 2001 Oct;183(19):5733-42
references.pmid: 11544237
references.citation: Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21
references.pmid: 11309499
references.citation: Environ Microbiol. 2007 Oct;9(10):2486-95
references.pmid: 17803774
references.citation: Philos Trans R Soc Lond B Biol Sci. 2007 Jul 29;362(1483):1119-34
references.pmid: 17360280
references.citation: Mol Microbiol. 2001 Nov;42(3):777-93
references.pmid: 11722742
references.citation: Appl Environ Microbiol. 2000 May;66(5):2079-84
references.pmid: 10788385
references.citation: Curr Opin Investig Drugs. 2005 Feb;6(2):178-84
references.pmid: 15751741
references.citation: Nat Rev Drug Discov. 2003 Feb;2(2):114-22
references.pmid: 12563302
references.citation: Microbiology (Reading). 2000 Dec;146 Pt 12:3237-3244
references.pmid: 11101681
references.citation: Mol Microbiol. 2003 Aug;49(3):581-90
references.pmid: 12864845
references.citation: Environ Microbiol. 2002 Jan;4(1):18-28
references.pmid: 11966822
references.citation: Sci Prog. 2006;89(Pt 3-4):167-211
references.pmid: 17338438
references.citation: Appl Environ Microbiol. 1996 Nov;62(11):4284-7
references.pmid: 16535454