title: Interfering with Bacterial Quorum Sensing.
abstract: Quorum sensing (QS) describes the exchange of chemical signals in bacterial populations to adjust the bacterial phenotypes according to the density of bacterial cells. This serves to express phenotypes that are advantageous for the group and ensure bacterial survival. To do so, bacterial cells synthesize autoinducer (AI) molecules, release them to the environment, and take them up. Thereby, the AI concentration reflects the cell density. When the AI concentration exceeds a critical threshold in the cells, the AI may activate the expression of virulence-associated genes or of luminescent proteins. It has been argued that targeting the QS system puts less selective pressure on these pathogens and should avoid the development of resistant bacteria. Therefore, the molecular components of QS systems have been suggested as promising targets for developing new anti-infective compounds. Here, we review the QS systems of selected gram-negative and gram-positive bacteria, namely, Vibrio fischeri, Pseudomonas aeruginosa, and Staphylococcus aureus, and discuss various antivirulence strategies based on blocking different components of the QS machinery.
authors.affiliation: Center for Bioinformatics, Saarland University, Saarbrücken, Germany.; Saarbrücken Graduate School of Computer Science, Saarland University, Saarbrücken, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Reuter
authors.affiliation: Department of Drug Design and Optimization, Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Saarland University, Saarbrücken, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Steinbach
authors.affiliation: Center for Bioinformatics, Saarland University, Saarbrücken, Germany.
authors.forename: Volkhard
authors.initials: V
authors.lastname: Helms
keywords: Pseudomonas aeruginoas; Staphylococcus aureus; Vibrio fischeri; autoinducer; quorum sensing inhibitors; virulence
references.citation: Chem Biol. 2007 Oct;14(10):1119-27
references.pmid: 17961824
references.citation: Biochemistry. 2012 Dec 18;51(50):10035-43
references.pmid: 23181972
references.citation: Nucleic Acids Res. 2015 Apr 20;43(7):3872
references.pmid: 25824943
references.citation: PLoS Pathog. 2014 Feb 13;10(2):e1003871
references.pmid: 24550724
references.citation: Eur J Med Chem. 2015 Jan 27;90:351-9
references.pmid: 25437621
references.citation: J Med Chem. 2015 Feb 12;58(3):1298-306
references.pmid: 25597392
references.citation: Biomacromolecules. 2010 Apr 12;11(4):975-80
references.pmid: 20230030
references.citation: Biotechnol Lett. 2013 Apr;35(4):631-7
references.pmid: 23264268
references.citation: Antimicrob Agents Chemother. 2015 Apr;59(4):2223-35
references.pmid: 25645827
references.citation: Nat Rev Microbiol. 2014 Jan;12(1):49-62
references.pmid: 24336184
references.citation: PLoS One. 2012;7(7):e39390
references.pmid: 22844393
references.citation: Cell. 2004 Jul 9;118(1):69-82
references.pmid: 15242645
references.citation: J Bacteriol. 1995 Feb;177(3):654-9
references.pmid: 7836299
references.citation: Microbiol Rev. 1991 Mar;55(1):123-42
references.pmid: 2030669
references.citation: Bioorg Med Chem. 2011 Aug 15;19(16):4812-9
references.pmid: 21798749
references.citation: Clin Microbiol Rev. 2009 Oct;22(4):582-610
references.pmid: 19822890
references.citation: J Bacteriol. 2008 Feb;190(4):1247-55
references.pmid: 18083812
references.citation: Proc Natl Acad Sci U S A. 2006 May 30;103(22):8487-92
references.pmid: 16687478
references.citation: J Bacteriol. 2005 Jul;187(13):4372-80
references.pmid: 15968046
references.citation: Annu Rev Microbiol. 1996;50:591-624
references.pmid: 8905092
references.citation: Antimicrob Agents Chemother. 2011 Jun;55(6):2655-61
references.pmid: 21422204
references.citation: PLoS Pathog. 2013 Feb;9(2):e1003166
references.pmid: 23459693
references.citation: Bioorg Med Chem. 2011 Aug 15;19(16):4820-8
references.pmid: 21798746
references.citation: Annu Rev Biomed Eng. 2008;10:145-67
references.pmid: 18647113
references.citation: Microbiology. 2001 Dec;147(Pt 12):3249-62
references.pmid: 11739757
references.citation: Nucleic Acids Res. 2011 Jul;39(Web Server issue):W270-7
references.pmid: 21624888
references.citation: BMC Syst Biol. 2013 Aug 21;7:81
references.pmid: 23965312
references.citation: Clin Microbiol Rev. 2000 Jan;13(1):16-34, table of contents
references.pmid: 10627489
references.citation: Appl Environ Microbiol. 2007 Oct;73(19):6036-44
references.pmid: 17693565
references.citation: Chem Soc Rev. 2008 Jul;37(7):1337-46
references.pmid: 18568160
references.citation: Mol Microbiol. 2002 Feb;43(3):809-21
references.pmid: 11929534
references.citation: J Bacteriol. 2002 Dec;184(23):6472-80
references.pmid: 12426334
references.citation: J Am Chem Soc. 2013 May 29;135(21):7869-82
references.pmid: 23647400
references.citation: J Med Chem. 2013 Aug 8;56(15):6146-55
references.pmid: 23834469
references.citation: Lab Invest. 2000 Feb;80(2):209-19
references.pmid: 10701690
references.citation: PLoS Pathog. 2011 Aug;7(8):e1002192
references.pmid: 21829370
references.citation: Microbiol Mol Biol Rev. 2012 Mar;76(1):46-65
references.pmid: 22390972
references.citation: Org Biomol Chem. 2013 Feb 14;11(6):938-54
references.pmid: 23258305
references.citation: J Basic Microbiol. 2012 Dec;52(6):679-86
references.pmid: 22359266
references.citation: Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1639-44
references.pmid: 9990077
references.citation: Mol Microbiol. 1993 Aug;9(4):773-86
references.pmid: 8231809
references.citation: ACS Chem Biol. 2012 Sep 21;7(9):1496-501
references.pmid: 22765028
references.citation: Trends Microbiol. 2014 Dec;22(12):676-85
references.pmid: 25300477
references.citation: Science. 1997 Jun 27;276(5321):2027-30
references.pmid: 9197262
references.citation: Antimicrob Agents Chemother. 2009 Jun;53(6):2432-43
references.pmid: 19364871
references.citation: Mar Drugs. 2011 Dec;9(12):2537-52
references.pmid: 22363239
references.citation: PLoS Pathog. 2010 May 06;6(5):e1000883
references.pmid: 20463812
references.citation: Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11229-34
references.pmid: 10500159
references.citation: J Comput Aided Mol Des. 2012 Sep;26(9):1067-77
references.pmid: 22986632
references.citation: Bacteriol Rev. 1975 Dec;39(4):317-44
references.pmid: 1108866
references.citation: Mol Microbiol. 2011 May;80(4):951-65
references.pmid: 21392132
references.citation: J Am Chem Soc. 2007 Nov 7;129(44):13613-25
references.pmid: 17927181
references.citation: Proc Natl Acad Sci U S A. 2001 Sep 25;98 (20):11633-7
references.pmid: 11573001
references.citation: PLoS One. 2014 Nov 07;9(11):e111198
references.pmid: 25379726
references.citation: PLoS Pathog. 2007 Sep 14;3(9):1229-39
references.pmid: 17941706
references.citation: Biochemistry. 1981 Apr 28;20(9):2444-9
references.pmid: 7236614
references.citation: Mol Microbiol. 2007 Aug;65(3):780-98
references.pmid: 17608791
references.citation: J Am Chem Soc. 2015 Feb 4;137(4):1510-9
references.pmid: 25574853
references.citation: Eur Respir J. 2008 Sep;32(3):740-7
references.pmid: 18480102
references.citation: J Bacteriol. 2007 Jun;189(11):4320-4
references.pmid: 17384185
references.citation: PLoS Pathog. 2014 Jun 12;10(6):e1004174
references.pmid: 24945495
references.citation: Ann Rev Mar Sci. 2010;2:443-93
references.pmid: 21141672
references.citation: J Bacteriol. 2013 Sep;195(18):4013-9
references.pmid: 23836869
references.citation: Macromol Biosci. 2015 May;15(5):647-56
references.pmid: 25626858
references.citation: J Bacteriol. 1985 Sep;163(3):1210-4
references.pmid: 3897188
references.citation: Chem Biol. 2015 May 21;22(5):611-8
references.pmid: 25960261
references.citation: PLoS Pathog. 2014 Aug 21;10(8):e1004321
references.pmid: 25144274
references.citation: Angew Chem Int Ed Engl. 2014 Jan 20;53(4):1109-12
references.pmid: 24338917
references.citation: Rev Infect Dis. 1984 Sep-Oct;6 Suppl 3:S627-42
references.pmid: 6443765
references.citation: Paediatr Respir Rev. 2002 Jun;3(2):128-34
references.pmid: 12297059
references.citation: Infect Immun. 2006 Mar;74(3):1673-82
references.pmid: 16495538
references.citation: J Am Chem Soc. 2012 Oct 3;134(39):16143-6
references.pmid: 22992202
references.citation: Chem Biol. 2012 Mar 23;19(3):381-90
references.pmid: 22444593
references.citation: Antimicrob Agents Chemother. 2013 Nov;57(11):5629-41
references.pmid: 24002091
references.citation: Mol Microbiol. 2000 May;36(4):940-54
references.pmid: 10844680
references.citation: J Bacteriol. 1970 Oct;104(1):313-22
references.pmid: 5473898
references.citation: J Bacteriol. 2015 May;197(10 ):1747-56
references.pmid: 25755191
references.citation: Eur J Med Chem. 2014 Apr 9;76:343-51
references.pmid: 24589489
references.citation: Bioorg Med Chem Lett. 2008 Nov 15;18(22):5978-81
references.pmid: 18760602
references.citation: Sci Rep. 2014 Nov 28;4:7245
references.pmid: 25430794
references.citation: Clin Infect Dis. 2008 Jun 1;46 Suppl 5:S350-9
references.pmid: 18462090
references.citation: Expert Opin Drug Discov. 2014 Apr;9(4):353-66
references.pmid: 24597980
references.citation: Mol Microbiol. 1994 Jul;13(2):273-86
references.pmid: 7984107
references.citation: Antimicrob Agents Chemother. 2009 Nov;53(11):4891-7
references.pmid: 19721066
references.citation: J Biol Chem. 2005 Apr 29;280(17):16695-704
references.pmid: 15734745
references.citation: PLoS One. 2014 May 22;9(5):e96166
references.pmid: 24852379
references.citation: Trends Microbiol. 2013 Feb;21(2):73-81
references.pmid: 23140890
references.citation: Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12619-23
references.pmid: 7809088
references.citation: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D678-83
references.pmid: 16381957
references.citation: PLoS Pathog. 2013;9(7):e1003508
references.pmid: 23935486
references.citation: J Exp Med. 2008 Feb 18;205(2):287-94
references.pmid: 18268041
references.citation: J Med Chem. 2014 Mar 27;57(6):2813-9
references.pmid: 24592914
references.citation: J Bacteriol. 2004 Mar;186(6):1838-50
references.pmid: 14996815
references.citation: J Bacteriol. 2001 Sep;183(17):5187-97
references.pmid: 11489873
references.citation: Eur J Med Chem. 2015;96:14-21
references.pmid: 25874327
references.citation: J Bacteriol. 2004 Oct;186(20):6902-14
references.pmid: 15466044
references.citation: Nat Chem Biol. 2007 Sep;3(9):541-8
references.pmid: 17710100
references.citation: Nat Rev Drug Discov. 2013 Oct;12(10):791-808
references.pmid: 24080700
references.citation: Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8951-6
references.pmid: 12847292
references.citation: J Bacteriol. 2005 Jun;187(11):3620-9
references.pmid: 15901683
references.citation: Future Microbiol. 2010 Nov;5(11):1663-74
references.pmid: 21133688
references.citation: Biophys J. 2014 Jul 1;107(1):266-77
references.pmid: 24988360
references.citation: Annu Rev Microbiol. 2001;55:165-99
references.pmid: 11544353
references.citation: J Med Chem. 2013 Sep 12;56(17):6761-74
references.pmid: 23919758
references.citation: J Am Chem Soc. 2006 Mar 8;128(9):2802-3
references.pmid: 16506750
references.citation: Proc Natl Acad Sci U S A. 2013 Oct 29;110(44):17981-6
references.pmid: 24143808
references.citation: Infect Immun. 2011 May;79(5):1927-35
references.pmid: 21402769
references.citation: J Bacteriol. 1996 May;178(10):2897-901
references.pmid: 8631679
references.citation: Sensors (Basel). 2012;12 (5):6645-65
references.pmid: 22778662
references.citation: J Bacteriol. 1999 Feb;181(4):1203-10
references.pmid: 9973347
references.citation: Annu Rev Genet. 2009;43:197-222
references.pmid: 19686078
references.citation: Cell. 1983 Mar;32(3):773-81
references.pmid: 6831560
references.citation: Mol Microbiol. 1999 Jan;31(2):665-77
references.pmid: 10027982
references.citation: J Antimicrob Chemother. 2004 Jun;53(6):1054-61
references.pmid: 15117922
references.citation: Nature. 2002 Jan 31;415(6871):545-9
references.pmid: 11823863
references.citation: Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):20765-70
references.pmid: 24319092
references.citation: J Clin Invest. 2003 May;111(9):1265-73
references.pmid: 12727914
references.citation: Nucleic Acids Res. 2015 Jan;43(Database issue):D204-12
references.pmid: 25348405
references.citation: J Biol Chem. 2002 Sep 20;277(38):34736-42
references.pmid: 12122003
references.citation: Microbiol Rev. 1979 Dec;43(4):496-518
references.pmid: 396467
references.citation: Future Med Chem. 2014;6(18):2057-72
references.pmid: 25531968
references.citation: Nature. 2010 May 20;465(7296):346-9
references.pmid: 20485435
references.citation: Antimicrob Agents Chemother. 2013 Aug;57(8):3653-8
references.pmid: 23689715
references.citation: Bioinformatics. 2005 May 1;21(9):1751-3
references.pmid: 15691861
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3587-90
references.pmid: 14970327
references.citation: N Engl J Med. 1998 Aug 20;339(8):520-32
references.pmid: 9709046