MULTIPLE N-ACYL-L-HOMOSERINE LACTONE SIGNAL MOLECULES REGULATE PRODUCTION OF VIRULENCE DETERMINANTS AND SECONDARY METABOLITES IN PSEUDOMONAS-AERUGINOSA

被引:423
作者
WINSON, MK
CAMARA, M
LATIFI, A
FOGLINO, M
CHHABRA, SR
DAYKIN, M
BALLY, M
CHAPON, V
SALMOND, GPC
BYCROFT, BW
LAZDUNSKI, A
STEWART, GSAB
WILLIAMS, P
机构
[1] UNIV NOTTINGHAM,DEPT PHARMACEUT SCI,NOTTINGHAM NG7 2RD,ENGLAND
[2] CNRS,INGN & DYNAM SYST MEMBRANAIRES LAB,F-13402 MARSEILLE 20,FRANCE
[3] UNIV WARWICK,DEPT BIOL SCI,COVENTRY CV4 7AL,W MIDLANDS,ENGLAND
[4] UNIV NOTTINGHAM,DEPT APPL BIOCHEM & FOOD SCI,NOTTINGHAM LE12 5RD,LEICS,ENGLAND
关键词
AUTOINDUCERS; QUORUM SENSING; GENE REGULATION;
D O I
10.1073/pnas.92.20.9427
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:9427 / 9431
页数:5
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