UNSPECIFIED (1995) MULTIPLE N-ACYL-L-HOMOSERINE LACTONE SIGNAL MOLECULES REGULATE PRODUCTION OF VIRULENCE DETERMINANTS AND SECONDARY METABOLITES IN PSEUDOMONAS-AERUGINOSA. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 92 (20). pp. 9427-9431. ISSN 0027-8424

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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 (WWL). These compounds are present in the spent culture supernatants of P, aeruginosa in a molar ratio of approximate to 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 fur reporter assay, These data indicate that multiple families of quorum sensing modulons interactively regulate gene expression in P. aeruginosa.

Item Type:	Journal Article
Subjects:	Q Science
Journal or Publication Title:	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Publisher:	NATL ACAD SCIENCES
ISSN:	0027-8424
Date:	26 September 1995
Volume:	92
Number:	20
Number of Pages:	5
Page Range:	pp. 9427-9431
Publication Status:	Published
URI:	http://wrap.warwick.ac.uk/id/eprint/19426

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