Structure of the Autoinducer Required for Expression of Pseudomonas Aeruginosa Virulence Genes

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1994 Jan 4

PMID 8278364

Citations 402

Authors

J P Pearson

K M Gray

L Passador

K D Tucker

A Eberhard

B H Iglewski

E P Greenberg

Affiliations

Soon will be listed here.

Abstract

In Pseudomonas aeruginosa the LasR protein is required for activation of lasB and several other virulence genes. A diffusible signal molecule, the P. aeruginosa autoinducer (PAI), produced by the bacterial cell and released into the growth medium, is required for activity of LasR. By cloning a lasB::lacZ fusion and a lasR gene under control of the lac promoter in Escherichia coli, we have developed a quantitative bioassay for PAI. We have used this assay to follow the purification of PAI from cell-free culture supernatant fluids in which P. aeruginosa or E. coli containing the P. aeruginosa gene required for autoinducer synthesis, lasI, had been grown. Chemical analyses indicated the purified material was 3-oxo-N-(tetrahydro-2-oxo-3-furanyl)dodecanamide. To confirm this assignment, the compound was synthesized and the synthetic compound was shown to have chemical and biological properties identical to those of PAI purified from culture supernatant fluids. The elucidation of the PAI structure suggests therapeutic approaches toward control of P. aeruginosa infections.

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References

Hanahan D . Studies on transformation of Escherichia coli with plasmids. J Mol Biol. 1983; 166(4):557-80. DOI: 10.1016/s0022-2836(83)80284-8. View

Engebrecht J, Silverman M . Identification of genes and gene products necessary for bacterial bioluminescence. Proc Natl Acad Sci U S A. 1984; 81(13):4154-8. PMC: 345387. DOI: 10.1073/pnas.81.13.4154. View

Kaplan H, Greenberg E . Diffusion of autoinducer is involved in regulation of the Vibrio fischeri luminescence system. J Bacteriol. 1985; 163(3):1210-4. PMC: 219261. DOI: 10.1128/jb.163.3.1210-1214.1985. View

Ralling G, Bodrug S, Linn T . Growth rate-dependent regulation of RNA polymerase synthesis in Escherichia coli. Mol Gen Genet. 1985; 201(3):379-86. DOI: 10.1007/BF00331327. View

Eberhard A, Widrig C, McBath P, Schineller J . Analogs of the autoinducer of bioluminescence in Vibrio fischeri. Arch Microbiol. 1986; 146(1):35-40. DOI: 10.1007/BF00690155. View

Goswami A, Beale Jr J, Chapman R, Miller D, Rosazza J . Microbial hydroxylation of quadrone to 8a-hydroxyquadrone. J Nat Prod. 1987; 50(1):49-54. DOI: 10.1021/np50049a008. View

Stewart V, Parales Jr J . Identification and expression of genes narL and narX of the nar (nitrate reductase) locus in Escherichia coli K-12. J Bacteriol. 1988; 170(4):1589-97. PMC: 211006. DOI: 10.1128/jb.170.4.1589-1597.1988. View

Bever R, Iglewski B . Molecular characterization and nucleotide sequence of the Pseudomonas aeruginosa elastase structural gene. J Bacteriol. 1988; 170(9):4309-14. PMC: 211443. DOI: 10.1128/jb.170.9.4309-4314.1988. View

Kessler E, Safrin M . Synthesis, processing, and transport of Pseudomonas aeruginosa elastase. J Bacteriol. 1988; 170(11):5241-7. PMC: 211597. DOI: 10.1128/jb.170.11.5241-5247.1988. View

10.

Cao J, Meighen E . Purification and structural identification of an autoinducer for the luminescence system of Vibrio harveyi. J Biol Chem. 1989; 264(36):21670-6. View

11.

Schweizer H . Escherichia-Pseudomonas shuttle vectors derived from pUC18/19. Gene. 1991; 97(1):109-21. DOI: 10.1016/0378-1119(91)90016-5. View

12.

Gambello M, Iglewski B . Cloning and characterization of the Pseudomonas aeruginosa lasR gene, a transcriptional activator of elastase expression. J Bacteriol. 1991; 173(9):3000-9. PMC: 207884. DOI: 10.1128/jb.173.9.3000-3009.1991. View

13.

Toder D, Gambello M, Iglewski B . Pseudomonas aeruginosa LasA: a second elastase under the transcriptional control of lasR. Mol Microbiol. 1991; 5(8):2003-10. DOI: 10.1111/j.1365-2958.1991.tb00822.x. View

14.

Brumlik M, Storey D . Zinc and iron regulate translation of the gene encoding Pseudomonas aeruginosa elastase. Mol Microbiol. 1992; 6(3):337-44. DOI: 10.1111/j.1365-2958.1992.tb01476.x. View

15.

Gray K, Greenberg E . Physical and functional maps of the luminescence gene cluster in an autoinducer-deficient Vibrio fischeri strain isolated from a squid light organ. J Bacteriol. 1992; 174(13):4384-90. PMC: 206223. DOI: 10.1128/jb.174.13.4384-4390.1992. View

16.

Bainton N, Bycroft B, Chhabra S, Stead P, Gledhill L, Hill P . A general role for the lux autoinducer in bacterial cell signalling: control of antibiotic biosynthesis in Erwinia. Gene. 1992; 116(1):87-91. DOI: 10.1016/0378-1119(92)90633-z. View

17.

Bainton N, Stead P, Chhabra S, Bycroft B, Salmond G, Stewart G . N-(3-oxohexanoyl)-L-homoserine lactone regulates carbapenem antibiotic production in Erwinia carotovora. Biochem J. 1992; 288 ( Pt 3):997-1004. PMC: 1131986. DOI: 10.1042/bj2880997. View

18.

Gambello M, Kaye S, Iglewski B . LasR of Pseudomonas aeruginosa is a transcriptional activator of the alkaline protease gene (apr) and an enhancer of exotoxin A expression. Infect Immun. 1993; 61(4):1180-4. PMC: 281346. DOI: 10.1128/iai.61.4.1180-1184.1993. View

19.

Zhang L, Murphy P, Kerr A, Tate M . Agrobacterium conjugation and gene regulation by N-acyl-L-homoserine lactones. Nature. 1993; 362(6419):446-8. DOI: 10.1038/362446a0. View

20.

Piper K, Beck von Bodman S, Farrand S . Conjugation factor of Agrobacterium tumefaciens regulates Ti plasmid transfer by autoinduction. Nature. 1993; 362(6419):448-50. DOI: 10.1038/362448a0. View