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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 (HHlL). These compounds are present in the spent culture supernatants of P. aeruginosa in a molar ratio of-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. The recognition that N-(3-oxohexanoyl)-L-homoserine lactone (OHHL; Fig. 1), previously termed the lux autoinducer (AI) (1), regulates both secondary metabolism (2, 3) and virulence in the plant pathogen Erwinia carotovora (4, 5) has been followed by a surge of interest in the role of N-acyl-L-homoserine lactones (AHLs) in bacterial gene expression (6-8). Diverse Gram-negative bacteria are now known to synthesize AHLs which form part of a cell-cell communication system that facilitates the induction of genetic regulons only when a significant cell population density has been attained (2, 6-8). This cell density dependency reflects the accumulation of the signal molecule to a critical threshold concentration (1, 6-8) and is termed quorum sensing (6). Quorum sensing systems depend upon the interaction of an Al, the synthesis of which is directed by a LuxI homologue, with a positive N HH
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Michael W Winson, Miguel Camara, Amel Latifi, Maryline Foglino, Ram Siri Chhabrat, et al.. Multiple N-acyl-L-homoserine lactone signal molecules regulate production of virulence determinants and secondary metabolites in Pseudomonas aeruginosa . Microbiology, 1995, 92 (20), pp.9427 - 9431. ⟨hal-01560869⟩



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