title: Indole production promotes Escherichia coli mixed-culture growth with Pseudomonas aeruginosa by inhibiting quorum signaling.
abstract: Indole production by Escherichia coli, discovered in the early 20th century, has been used as a diagnostic marker for distinguishing E. coli from other enteric bacteria. By using transcriptional profiling and competition studies with defined mutants, we show that cyclic AMP (cAMP)-regulated indole formation is a major factor that enables E. coli growth in mixed biofilm and planktonic populations with Pseudomonas aeruginosa. Mutants deficient in cAMP production (cyaA) or the cAMP receptor gene (crp), as well as indole production (tnaA), were not competitive in coculture with P. aeruginosa but could be restored to wild-type competitiveness by supplementation with a physiologically relevant indole concentration. E. coli sdiA mutants, which lacked the receptor for both indole and N-acyl-homoserine lactones (AHLs), showed no change in competitive fitness, suggesting that indole acted directly on P. aeruginosa. An E. coli tnaA mutant strain regained wild-type competiveness if grown with P. aeruginosa AHL synthase (rhlI and rhlI lasI) mutants. In contrast to the wild type, P. aeruginosa AHL synthase mutants were unable to degrade indole. Indole produced during mixed-culture growth inhibited pyocyanin production and other AHL-regulated virulence factors in P. aeruginosa. Mixed-culture growth with P. aeruginosa stimulated indole formation in E. coli cpdA, which is unable to regulate cAMP levels, suggesting the potential for mixed-culture gene activation via cAMP. These findings illustrate how indole, an early described feature of E. coli central metabolism, can play a significant role in mixed-culture survival by inhibiting quorum-regulated competition factors in P. aeruginosa.
authors.affiliation: Department of Microbiology, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Chu
authors.forename: Tesfalem R
authors.initials: TR
authors.lastname: Zere
authors.forename: Mary M
authors.initials: MM
authors.lastname: Weber
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Wood
authors.forename: Marvin
authors.initials: M
authors.lastname: Whiteley
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hidalgo-Romano
authors.forename: Ernesto
authors.initials: E
authors.lastname: Valenzuela
authors.forename: Robert J C
authors.initials: RJ
authors.lastname: McLean
mesh_terms: D000242:Cyclic AMP / Q000378:metabolism; D004926:Escherichia coli / Q000254:growth & development* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D020869:Gene Expression Profiling; D007211:Indoles / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000254:growth & development* / Q000378:metabolism*; D053038:Quorum Sensing; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D029968:Escherichia coli Proteins; D007211:Indoles; C030374:indole; D000242:Cyclic AMP
references.citation: J Bacteriol. 2007 Sep;189(17):6407-14
references.pmid: 17586632
references.citation: J Bacteriol. 2001 Jul;183(14):4210-6
references.pmid: 11418561
references.citation: BMC Microbiol. 2007 Jun 08;7:53
references.pmid: 17559662
references.citation: Environ Microbiol. 2011 Jan;13(1):62-73
references.pmid: 20649646
references.citation: Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):336-41
references.pmid: 8552633
references.citation: Phytomedicine. 2010 Nov;17(13):1040-6
references.pmid: 20554187
references.citation: Nature. 2011 Jul 20;475(7356):343-7
references.pmid: 21776080
references.citation: J Bacteriol. 2005 Jan;187(2):554-66
references.pmid: 15629927
references.citation: Microbiology (Reading). 2002 Apr;148(Pt 4):923-932
references.pmid: 11932439
references.citation: J Physiol. 1903 Jun 15;29(4-5):451-66
references.pmid: 16992682
references.citation: ISME J. 2008 Oct;2(10):1007-23
references.pmid: 18528414
references.citation: J Bacteriol. 2009 Oct;191(19):6094-104
references.pmid: 19633076
references.citation: Microbiology (Reading). 2007 May;153(Pt 5):1329-1338
references.pmid: 17464047
references.citation: J Bacteriol. 2005 Aug;187(15):5267-77
references.pmid: 16030221
references.citation: J Biol Chem. 1996 Oct 11;271(41):25423-9
references.pmid: 8810311
references.citation: Science. 1997 Sep 5;277(5331):1453-62
references.pmid: 9278503
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1578-83
references.pmid: 19164580
references.citation: Mol Syst Biol. 2006;2:2006.0008
references.pmid: 16738554
references.citation: Microbiol Mol Biol Rev. 2006 Jun;70(2):564-82
references.pmid: 16760314
references.citation: Nat Rev Microbiol. 2008 Sep;6(9):657-66
references.pmid: 18679171
references.citation: Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9427-31
references.pmid: 7568146
references.citation: Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13904-9
references.pmid: 10570171
references.citation: mBio. 2010 Sep 21;1(4):
references.pmid: 20856824
references.citation: Proc Natl Acad Sci U S A. 1974 Apr;71(4):1436-40
references.pmid: 4364540
references.citation: Nature. 2005 Sep 15;437(7057):422-5
references.pmid: 16163359
references.citation: Microbiol Rev. 1992 Mar;56(1):100-22
references.pmid: 1315922
references.citation: J Bacteriol. 1990 Feb;172(2):884-900
references.pmid: 2153661
references.citation: Microbiology (Reading). 1994 Aug;140 ( Pt 8):2125-34
references.pmid: 7921262
references.citation: ACS Chem Biol. 2009 Aug 21;4(8):617-23
references.pmid: 19621937
references.citation: J Bacteriol. 1980 Jan;141(1):156-63
references.pmid: 6243619
references.citation: Microbiology (Reading). 2010 Jan;156(Pt 1):139-147
references.pmid: 19833773
references.citation: Microb Biotechnol. 2009 Jan;2(1):75-90
references.pmid: 21261883
references.citation: Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11229-34
references.pmid: 10500159
references.citation: EMBO J. 2003 Aug 1;22(15):3803-15
references.pmid: 12881415
references.citation: J Bacteriol. 2004 Aug;186(15):4921-30
references.pmid: 15262929
references.citation: Int Rev Cytol. 1981;72:229-317
references.pmid: 6166584
references.citation: Can J Microbiol. 2002 Jul;48(7):675-80
references.pmid: 12224565
references.citation: FEMS Microbiol Lett. 1999 Oct 15;179(2):345-52
references.pmid: 10518736
references.citation: Nature. 2000 Aug 31;406(6799):959-64
references.pmid: 10984043
references.citation: Annu Rev Genet. 2009;43:197-222
references.pmid: 19686078
references.citation: Appl Environ Microbiol. 2011 Feb;77(3):821-9
references.pmid: 21131510
references.citation: J Bacteriol. 2000 Nov;182(21):5990-6
references.pmid: 11029417
references.citation: Nat Rev Microbiol. 2009 Apr;7(4):263-73
references.pmid: 19287449
references.citation: BMC Microbiol. 2007 May 18;7:42
references.pmid: 17511876
references.citation: Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3828-33
references.pmid: 16537456
references.citation: Appl Environ Microbiol. 2009 Mar;75(6):1703-16
references.pmid: 19168658
references.citation: Appl Environ Microbiol. 1999 Sep;65(9):4285-7
references.pmid: 10473455
references.citation: J Bacteriol. 2004 Jun;186(11):3516-24
references.pmid: 15150239