title: The Agr quorum-sensing system regulates fibronectin binding but not hemolysis in the absence of a functional electron transport chain.
abstract: Staphylococcus aureus is responsible for numerous chronic and recurrent infections, which are frequently associated with the emergence of small-colony variants (SCVs) that lack a functional electron transport chain. SCVs exhibit enhanced expression of fibronectin-binding protein (FnBP) and greatly reduced hemolysin production, although the basis for this is unclear. One hypothesis is that these phenotypes are a consequence of the reduced Agr activity of SCVs, while an alternative is that the lack of a functional electron transport chain and the resulting reduction in ATP production are responsible. Disruption of the electron transport chain of S. aureus genetically (hemB and menD) or chemically, using 2-n-heptyl-4-hydroxyquinoline N-oxide (HQNO), inhibited both growth and Agr activity and conferred an SCV phenotype. Supplementation of the culture medium with synthetic autoinducing peptide (sAIP) significantly increased Agr expression in both hemB mutant strains and S. aureus grown with HQNO and significantly reduced staphylococcal adhesion to fibronectin. However, sAIP did not promote hemolysin expression in hemB mutant strains or S. aureus grown with HQNO. Therefore, while Agr regulates fibronectin binding in SCVs, it cannot promote hemolysin production in the absence of a functional electron transport chain.
authors.affiliation: Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
authors.forename: Vera
authors.initials: V
authors.lastname: Pader
authors.affiliation: Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
authors.forename: Ellen H
authors.initials: EH
authors.lastname: James
authors.affiliation: Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
authors.forename: Kimberley L
authors.initials: KL
authors.lastname: Painter
authors.affiliation: Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
authors.forename: Sivaramesh
authors.initials: S
authors.lastname: Wigneshweraraj
authors.affiliation: Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom a.edwards@imperial.ac.uk.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Edwards
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D004579:Electron Transport; D005353:Fibronectins / Q000378:metabolism*; D006461:Hemolysis; D006801:Humans; D011485:Protein Binding; D053038:Quorum Sensing; D013211:Staphylococcus aureus / Q000378:metabolism / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D005353:Fibronectins; D015534:Trans-Activators
references.citation: J Bacteriol. 1997 Aug;179(15):4706-12
references.pmid: 9244256
references.citation: Infect Immun. 2014 Apr;82(4):1600-5
references.pmid: 24452687
references.citation: J Infect Dis. 1998 Apr;177(4):1023-9
references.pmid: 9534977
references.citation: Mol Gen Genet. 1986 Jan;202(1):58-61
references.pmid: 3007938
references.citation: PLoS One. 2013 May 21;8(5):e65018
references.pmid: 23705029
references.citation: J Clin Invest. 1994 Nov;94(5):1815-22
references.pmid: 7962526
references.citation: FEMS Microbiol Lett. 2013 Dec;349(2):153-62
references.pmid: 24164684
references.citation: Mol Microbiol. 2005 Mar;55(5):1591-605
references.pmid: 15720563
references.citation: PLoS Pathog. 2010 Jun 24;6(6):e1000964
references.pmid: 20585570
references.citation: mBio. 2013 Nov 12;4(6):e00696-13
references.pmid: 24222487
references.citation: Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6462-6
references.pmid: 1321441
references.citation: Antimicrob Agents Chemother. 2002 Aug;46(8):2333-6
references.pmid: 12121901
references.citation: Clin Infect Dis. 2006 Oct 15;43(8):961-7
references.pmid: 16983605
references.citation: Microbiol Mol Biol Rev. 2009 Jun;73(2):233-48
references.pmid: 19487727
references.citation: J Infect Dis. 2010 Oct 1;202(7):1031-40
references.pmid: 20715929
references.citation: Antimicrob Agents Chemother. 2006 Apr;50(4):1183-94
references.pmid: 16569828
references.citation: Proteomics. 2012 Jan;12(2):263-8
references.pmid: 22106056
references.citation: Infect Immun. 2002 Oct;70(10):5428-37
references.pmid: 12228267
references.citation: Mol Microbiol. 2001 Jul;41(2):503-12
references.pmid: 11489134
references.citation: J Bacteriol. 2001 Feb;183(4):1113-23
references.pmid: 11157922
references.citation: Pediatr Infect Dis J. 2007 Mar;26(3):269-71
references.pmid: 17484231
references.citation: Microb Drug Resist. 2002 Winter;8(4):253-60
references.pmid: 12523621
references.citation: mBio. 2012 Mar 20;3(2):
references.pmid: 22434850
references.citation: Nat Rev Microbiol. 2014 Jan;12(1):49-62
references.pmid: 24336184
references.citation: Am J Surg. 2011 Feb;201(2):216-20
references.pmid: 20832054
references.citation: J Bacteriol. 2006 Jan;188(1):64-76
references.pmid: 16352822
references.citation: Infection. 2000 Jan-Feb;28(1):53-4
references.pmid: 10697795
references.citation: Infect Immun. 2010 Jun;78(6):2877-89
references.pmid: 20212089
references.citation: FEMS Immunol Med Microbiol. 2002 Feb 18;32(3):191-7
references.pmid: 11934563
references.citation: J Bacteriol. 2008 Feb;190(3):834-42
references.pmid: 17905979
references.citation: Am J Orthop (Belle Mead NJ). 2012 Mar;41(3):117-22
references.pmid: 22530208
references.citation: N Engl J Med. 1998 Aug 20;339(8):520-32
references.pmid: 9709046
references.citation: Mol Microbiol. 2003 Aug;49(4):919-27
references.pmid: 12890018
references.citation: J Infect. 2000 Jul;41(1):23-31
references.pmid: 10942636
references.citation: Annu Rev Genet. 2008;42:541-64
references.pmid: 18713030
references.citation: J Infect Dis. 2003 May 15;187(10):1654-61
references.pmid: 12721946
references.citation: Biochemistry. 2007 Jan 9;46(1):314-21
references.pmid: 17198402
references.citation: Clin Microbiol Infect. 2010 Jul;16(7):798-808
references.pmid: 20880409
references.citation: J Bacteriol. 2012 Oct;194(19):5404-12
references.pmid: 22865841
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19890-5
references.pmid: 17172450
references.citation: Infect Immun. 2009 May;77(5):1968-75
references.pmid: 19273557
references.citation: Clin Infect Dis. 2008 Jun 1;46 Suppl 5:S350-9
references.pmid: 18462090
references.citation: J Bacteriol. 2014 Mar;196(6):1184-96
references.pmid: 24391052
references.citation: J Bacteriol. 2004 Apr;186(8):2430-8
references.pmid: 15060046
references.citation: Br J Biomed Sci. 2000;57(4):317-22
references.pmid: 11204864
references.citation: Infect Immun. 1998 Nov;66(11):5238-43
references.pmid: 9784528
references.citation: PLoS One. 2011;6(9):e24301
references.pmid: 21912685
references.citation: J Bacteriol. 2006 Nov;188(22):7765-77
references.pmid: 16980462
references.citation: Nat Rev Microbiol. 2006 Apr;4(4):295-305
references.pmid: 16541137
references.citation: EMBO J. 1990 May;9(5):1391-9
references.pmid: 2328718
references.citation: Infect Immun. 1998 May;66(5):1869-77
references.pmid: 9573063
references.citation: PLoS One. 2010 Dec 28;5(12):e14431
references.pmid: 21203439
references.citation: Antimicrob Agents Chemother. 2008 Nov;52(11):4017-22
references.pmid: 18779359
references.citation: Emerg Infect Dis. 1999 May-Jun;5(3):450-3
references.pmid: 10341185
references.citation: J Bacteriol. 2005 Nov;187(21):7397-406
references.pmid: 16237023
references.citation: EMBO Mol Med. 2011 Mar;3(3):129-41
references.pmid: 21268281
references.citation: J Bacteriol. 2009 May;191(9):2953-63
references.pmid: 19251851
references.citation: EMBO J. 1993 Oct;12(10):3967-75
references.pmid: 7691599
references.citation: Lancet. 2006 Mar 4;367(9512):731-9
references.pmid: 16517273
references.citation: Int J Med Microbiol. 2007 Jul;297(4):217-25
references.pmid: 17412637
references.citation: Int J Med Microbiol. 2013 Dec;303(8):685-92
references.pmid: 24183484
references.citation: Infect Genet Evol. 2014 Jan;21:515-22
references.pmid: 23722021
references.citation: FEMS Immunol Med Microbiol. 2000 Sep;29(1):39-45
references.pmid: 10967259
references.citation: Nat Rev Microbiol. 2005 Dec;3(12):948-58
references.pmid: 16322743
references.citation: PLoS Pathog. 2012;8(11):e1003016
references.pmid: 23209405
references.citation: Clin Infect Dis. 1995 Jan;20(1):95-102
references.pmid: 7727677
references.citation: Clin Infect Dis. 2001 Jun 1;32(11):1643-7
references.pmid: 11340539
references.citation: J Bacteriol. 2002 Oct;184(19):5457-67
references.pmid: 12218034
references.citation: J Bacteriol. 1997 Sep;179(17):5259-63
references.pmid: 9286974
references.citation: Curr Opin Pulm Med. 2011 Nov;17(6):437-41
references.pmid: 21918450