• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Sep 26, 1995; 92(20): 9427–9431.
PMCID: PMC40998

Multiple N-acyl-L-homoserine lactone signal molecules regulate production of virulence determinants and secondary metabolites in Pseudomonas aeruginosa.

Abstract

Pseudomonas aeruginosa produces a spectrum of exoproducts many of which have been implicated in the pathogenesis of human infection. Expression of some of these factors requires cell-cell communication involving the interaction of a small diffusible molecule, an "autoinducer," with a positive transcriptional activator. In P. aeruginosa PAO1, LasI directs the synthesis of the autoinducer N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL), which activates the positive transcriptional activator, LasR. Recently, we have discovered a second signaling molecule-based modulon in PAO1, termed vsm, which contains the genes vsmR and vsmI. Using HPLC, mass spectrometry, and NMR spectroscopy we now establish that in Escherichia coli, VsmI directs the synthesis of N-butanoyl-L-homoserine lactone (BHL) and N-hexanoyl-L-homoserine lactone (HHL). These compounds are present in the spent culture supernatants of P. aeruginosa in a molar ratio of approximately 15:1 and their structures were unequivocally confirmed by chemical synthesis. Addition of either BHL or HHL to PAN067, a pleiotropic P. aeruginosa mutant unable to synthesize either of these autoinducers, restored elastase, chitinase, and cyanide production. In E. coli carrying a vsmR/vsmI'::lux transcriptional fusion, BHL and HHL activated VsmR to a similar extent. Analogues of these N-acyl-L-homoserine lactones in which the N-acyl side chain has been extended and/or oxidized at the C-3 position exhibit substantially lower activity (e.g., OdDHL) or no activity (e.g., dDHL) in this lux reporter assay. These data indicate that multiple families of quorum sensing modulons interactively regulate gene expression in P. aeruginosa.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Meighen EA. Molecular biology of bacterial bioluminescence. Microbiol Rev. 1991 Mar;55(1):123–142. [PMC free article] [PubMed]
  • Bainton NJ, Bycroft BW, Chhabra SR, Stead P, Gledhill L, Hill PJ, Rees CE, Winson MK, Salmond GP, Stewart GS, et al. A general role for the lux autoinducer in bacterial cell signalling: control of antibiotic biosynthesis in Erwinia. Gene. 1992 Jul 1;116(1):87–91. [PubMed]
  • Bainton NJ, Stead P, Chhabra SR, Bycroft BW, Salmond GP, Stewart GS, Williams P. N-(3-oxohexanoyl)-L-homoserine lactone regulates carbapenem antibiotic production in Erwinia carotovora. Biochem J. 1992 Dec 15;288(Pt 3):997–1004. [PMC free article] [PubMed]
  • Jones S, Yu B, Bainton NJ, Birdsall M, Bycroft BW, Chhabra SR, Cox AJ, Golby P, Reeves PJ, Stephens S, et al. The lux autoinducer regulates the production of exoenzyme virulence determinants in Erwinia carotovora and Pseudomonas aeruginosa. EMBO J. 1993 Jun;12(6):2477–2482. [PMC free article] [PubMed]
  • Pirhonen M, Flego D, Heikinheimo R, Palva ET. A small diffusible signal molecule is responsible for the global control of virulence and exoenzyme production in the plant pathogen Erwinia carotovora. EMBO J. 1993 Jun;12(6):2467–2476. [PMC free article] [PubMed]
  • Fuqua WC, Winans SC, Greenberg EP. Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators. J Bacteriol. 1994 Jan;176(2):269–275. [PMC free article] [PubMed]
  • Swift S, Bainton NJ, Winson MK. Gram-negative bacterial communication by N-acyl homoserine lactones: a universal language? Trends Microbiol. 1994 Jun;2(6):193–198. [PubMed]
  • Salmond GP, Bycroft BW, Stewart GS, Williams P. The bacterial 'enigma': cracking the code of cell-cell communication. Mol Microbiol. 1995 May;16(4):615–624. [PubMed]
  • Swift S, Winson MK, Chan PF, Bainton NJ, Birdsall M, Reeves PJ, Rees CE, Chhabra SR, Hill PJ, Throup JP, et al. A novel strategy for the isolation of luxI homologues: evidence for the widespread distribution of a LuxR:LuxI superfamily in enteric bacteria. Mol Microbiol. 1993 Nov;10(3):511–520. [PubMed]
  • McGowan S, Sebaihia M, Jones S, Yu B, Bainton N, Chan PF, Bycroft B, Stewart GS, Williams P, Salmond GP. Carbapenem antibiotic production in Erwinia carotovora is regulated by CarR, a homologue of the LuxR transcriptional activator. Microbiology. 1995 Mar;141(Pt 3):541–550. [PubMed]
  • Fuqua WC, Winans SC. A LuxR-LuxI type regulatory system activates Agrobacterium Ti plasmid conjugal transfer in the presence of a plant tumor metabolite. J Bacteriol. 1994 May;176(10):2796–2806. [PMC free article] [PubMed]
  • Piper KR, Beck von Bodman S, Farrand SK. Conjugation factor of Agrobacterium tumefaciens regulates Ti plasmid transfer by autoinduction. Nature. 1993 Apr 1;362(6419):448–450. [PubMed]
  • Hwang I, Li PL, Zhang L, Piper KR, Cook DM, Tate ME, Farrand SK. TraI, a LuxI homologue, is responsible for production of conjugation factor, the Ti plasmid N-acylhomoserine lactone autoinducer. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4639–4643. [PMC free article] [PubMed]
  • Gambello MJ, Iglewski BH. Cloning and characterization of the Pseudomonas aeruginosa lasR gene, a transcriptional activator of elastase expression. J Bacteriol. 1991 May;173(9):3000–3009. [PMC free article] [PubMed]
  • Passador L, Cook JM, Gambello MJ, Rust L, Iglewski BH. Expression of Pseudomonas aeruginosa virulence genes requires cell-to-cell communication. Science. 1993 May 21;260(5111):1127–1130. [PubMed]
  • Ochsner UA, Koch AK, Fiechter A, Reiser J. Isolation and characterization of a regulatory gene affecting rhamnolipid biosurfactant synthesis in Pseudomonas aeruginosa. J Bacteriol. 1994 Apr;176(7):2044–2054. [PMC free article] [PubMed]
  • Pierson LS, 3rd, Keppenne VD, Wood DW. Phenazine antibiotic biosynthesis in Pseudomonas aureofaciens 30-84 is regulated by PhzR in response to cell density. J Bacteriol. 1994 Jul;176(13):3966–3974. [PMC free article] [PubMed]
  • Cubo MT, Economou A, Murphy G, Johnston AW, Downie JA. Molecular characterization and regulation of the rhizosphere-expressed genes rhiABCR that can influence nodulation by Rhizobium leguminosarum biovar viciae. J Bacteriol. 1992 Jun;174(12):4026–4035. [PMC free article] [PubMed]
  • Pearson JP, Gray KM, Passador L, Tucker KD, Eberhard A, Iglewski BH, Greenberg EP. Structure of the autoinducer required for expression of Pseudomonas aeruginosa virulence genes. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):197–201. [PMC free article] [PubMed]
  • Chhabra SR, Stead P, Bainton NJ, Salmond GP, Stewart GS, Williams P, Bycroft BW. Autoregulation of carbapenem biosynthesis in Erwinia carotovora by analogues of N-(3-oxohexanoyl)-L-homoserine lactone. J Antibiot (Tokyo) 1993 Mar;46(3):441–454. [PubMed]
  • Castric KF, Castric PA. Method for rapid detection of cyanogenic bacteria. Appl Environ Microbiol. 1983 Feb;45(2):701–702. [PMC free article] [PubMed]
  • Eberhard A, Burlingame AL, Eberhard C, Kenyon GL, Nealson KH, Oppenheimer NJ. Structural identification of autoinducer of Photobacterium fischeri luciferase. Biochemistry. 1981 Apr 28;20(9):2444–2449. [PubMed]
  • Zhang L, Murphy PJ, Kerr A, Tate ME. Agrobacterium conjugation and gene regulation by N-acyl-L-homoserine lactones. Nature. 1993 Apr 1;362(6419):446–448. [PubMed]
  • Kuo A, Blough NV, Dunlap PV. Multiple N-acyl-L-homoserine lactone autoinducers of luminescence in the marine symbiotic bacterium Vibrio fischeri. J Bacteriol. 1994 Dec;176(24):7558–7565. [PMC free article] [PubMed]
  • Gray KM, Passador L, Iglewski BH, Greenberg EP. Interchangeability and specificity of components from the quorum-sensing regulatory systems of Vibrio fischeri and Pseudomonas aeruginosa. J Bacteriol. 1994 May;176(10):3076–3080. [PMC free article] [PubMed]
  • Hwang I, Cook DM, Farrand SK. A new regulatory element modulates homoserine lactone-mediated autoinduction of Ti plasmid conjugal transfer. J Bacteriol. 1995 Jan;177(2):449–458. [PMC free article] [PubMed]
  • Gambello MJ, Kaye S, Iglewski BH. LasR of Pseudomonas aeruginosa is a transcriptional activator of the alkaline protease gene (apr) and an enhancer of exotoxin A expression. Infect Immun. 1993 Apr;61(4):1180–1184. [PMC free article] [PubMed]
  • Pearson JP, Passador L, Iglewski BH, Greenberg EP. A second N-acylhomoserine lactone signal produced by Pseudomonas aeruginosa. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1490–1494. [PMC free article] [PubMed]
  • Cao JG, Meighen EA. Purification and structural identification of an autoinducer for the luminescence system of Vibrio harveyi. J Biol Chem. 1989 Dec 25;264(36):21670–21676. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...