title: Early activation of quorum sensing in Pseudomonas aeruginosa reveals the architecture of a complex regulon.
abstract: BACKGROUND
  Quorum-sensing regulation of gene expression in Pseudomonas aeruginosa is complex. Two interconnected acyl-homoserine lactone (acyl-HSL) signal-receptor pairs, 3-oxo-dodecanoyl-HSL-LasR and butanoyl-HSL-RhlR, regulate more than 300 genes. The induction of most of the genes is delayed during growth of P. aeruginosa in complex medium, cannot be advanced by addition of exogenous signal, and requires additional regulatory components. Many of these late genes can be induced by addition of signals early by using specific media conditions. While several factors super-regulate the quorum receptors, others may co-regulate target promoters or may affect expression posttranscriptionally.
  
  
  RESULTS
  To better understand the contributions of super-regulation and co-regulation to quorum-sensing gene expression, and to better understand the general structure of the quorum sensing network, we ectopically expressed the two receptors (in the presence of their cognate signals) and another component that affects quorum sensing, the stationary phase sigma factor RpoS, early in growth. We determined the effect on target gene expression by microarray and real-time PCR analysis. Our results show that many target genes (e.g. lasB and hcnABC) are directly responsive to receptor protein levels. Most genes (e.g. lasA, lecA, and phnAB), however, are not significantly affected, although at least some of these genes are directly regulated by quorum sensing. The majority of promoters advanced by RhlR appeared to be regulated directly, which allowed us to build a RhlR consensus sequence.
  
  
  CONCLUSIONS
  The direct responsiveness of many quorum sensing target genes to receptor protein levels early in growth confirms the role of super-regulation in quorum sensing gene expression. The observation that the induction of most target genes is not affected by signal or receptor protein levels indicates that either target promoters are co-regulated by other transcription factors, or that expression is controlled posttranscriptionally. This architecture permits the integration of multiple signaling pathways resulting in quorum responses that require a "quorum" but are otherwise highly adaptable and receptive to environmental conditions.
authors: Department of Microbiology, University of Washington, Box 357242, 1959 NE Pacific St, Seattle, WA 98195, USA. martin.schuster@oregonstate.edu
authors: Martin
authors: M
authors: Schuster
authors: E Peter
authors: EP
authors: Greenberg
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D016000:Cluster Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D005798:Genes, Bacterial; D020411:Oligonucleotide Array Sequence Analysis; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000254:growth & development; D053038:Quorum Sensing / Q000235:genetics*; D018085:Regulon / Q000502:physiology*; D012808:Sigma Factor / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C080365:LasR protein, Pseudomonas aeruginosa; D012808:Sigma Factor; D015534:Trans-Activators; C069567:sigma factor KatF protein, Bacteria
references: J Bacteriol. 2001 Nov;183(22):6676-83
references: 11673439
references: Gene. 1998 May 28;212(1):77-86
references: 9661666
references: Nat Genet. 2002 May;31(1):64-8
references: 11967538
references: Nat Rev Mol Cell Biol. 2002 Sep;3(9):685-95
references: 12209128
references: J Bacteriol. 2003 Jan;185(1):377-80
references: 12486077
references: Mol Microbiol. 2003 Feb;47(4):871-7
references: 12581345
references: Curr Opin Microbiol. 2003 Feb;6(1):56-60
references: 12615220
references: J Bacteriol. 2003 Apr;185(7):2061-5
references: 12644475
references: J Bacteriol. 2003 Apr;185(7):2066-79
references: 12644476
references: J Bacteriol. 2003 Apr;185(7):2080-95
references: 12644477
references: Nucleic Acids Res. 2003 Jul 1;31(13):3593-6
references: 12824373
references: EMBO J. 2003 Aug 1;22(15):3803-15
references: 12881415
references: Microbiology. 2003 Nov;149(Pt 11):3073-81
references: 14600219
references: Mol Microbiol. 2004 Feb;51(4):973-85
references: 14763974
references: Genomics. 2004 Mar;83(3):349-60
references: 14986705
references: J Bacteriol. 2004 May;186(10):2936-45
references: 15126453
references: Genome Res. 2004 Jun;14(6):1188-90
references: 15173120
references: Microbiol Rev. 1979 Mar;43(1):73-102
references: 111024
references: Mol Microbiol. 1996 Sep;21(6):1137-46
references: 8898383
references: Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13904-9
references: 10570171
references: Plasmid. 2000 Jan;43(1):59-72
references: 10610820
references: J Bacteriol. 2000 Aug;182(15):4356-60
references: 10894749
references: Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):8789-93
references: 10922036
references: J Bacteriol. 2000 Nov;182(22):6401-11
references: 11053384
references: Mol Microbiol. 2001 May;40(3):708-18
references: 11359576
references: J Bacteriol. 2001 Jun;183(12):3712-20
references: 11371535
references: FEMS Microbiol Rev. 2001 Aug;25(4):365-404
references: 11524130
references: J Bacteriol. 2001 Oct;183(19):5529-34
references: 11544214
references: J Bacteriol. 1997 May;179(10):3127-32
references: 9150205
references: Mol Microbiol. 1997 Apr;24(2):309-19
references: 9159518
references: J Bacteriol. 1997 Jun;179(12):3928-35
references: 9190808
references: Gene. 1997 Jun 3;191(2):149-53
references: 9218713
references: J Bacteriol. 1997 Sep;179(18):5756-67
references: 9294432
references: Gene. 1999 Feb 18;227(2):197-203
references: 10023058
references: Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11229-34
references: 10500159
references: Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15833-9
references: 15505212
references: Mol Microbiol. 2005 Feb;55(4):998-1014
references: 15686549
references: Environ Microbiol. 2005 Apr;7(4):459-71
references: 15816912
references: Proc Natl Acad Sci U S A. 2005 Jun 21;102(25):9008-13
references: 15956210
references: J Bacteriol. 2006 Jan;188(1):132-40
references: 16352829
references: Mol Microbiol. 2006 Jan;59(2):602-9
references: 16390453
references: Mol Microbiol. 2006 Mar;59(5):1542-58
references: 16468994
references: Int J Med Microbiol. 2006 Apr;296(2-3):73-81
references: 16476569
references: J Bacteriol. 2006 Aug;188(16):6026-33
references: 16885472
references: J Bacteriol. 2007 Jun;189(12):4367-74
references: 17449616
references: J Bacteriol. 2002 May;184(10):2576-86
references: 11976285