N-Acylhomoserine Lactones Undergo Lactonolysis in a pH-, Temperature-, and Acyl Chain Length-Dependent Manner during Growth of Yersinia pseudotuberculosis and Pseudomonas aeruginosa

摘要: In gram-negative bacterial pathogens, such as Pseudomonas aeruginosa and Yersinia pseudotuberculosis, cell-to-cell communication via the N-acylhomoserine lactone (AHL) signal molecules is involved in cell population density-dependent control of genes associated with virulence. This phenomenon, termed quorum sensing, relies upon accumulation AHLs to a threshold concentration at which target structural are activated. By using biosensors capable detecting range we observed that, cultures Y. pseudotuberculosis P. aeruginosa, accumulate during exponential phase but largely disappear stationary phase. When added late-stationary-phase, cell-free culture supernatants respective pathogen, major [N-butanoylhomoserine (C4-HSL) N-(3-oxododecanoyl)homoserine (3-oxo-C12-HSL)] [N-(3-oxohexanoyl)homoserine (3-oxo-C6-HSL) N-hexanoylhomoserine (C6-HSL)] were inactivated. Short-acyl-chain compounds (e.g., C4-HSL) turned over more extensively than long-chain 3-oxo-C12-HSL). Little AHL inactivation occurred extracts, no evidence for by specific enzymes was apparent. turnover discovered be due pH-dependent lactonolysis. acidifying growth media pH 2.0, lactonolysis could reversed. carbon-13 nuclear magnetic resonance spectroscopy, found that ring opening homoserine (HSL), N-propionyl HSL (C3-HSL), C4-HSL increased diminished N-acyl chain lengthened. At low levels, rings closed not simple reversal reaction mechanism. Ring C4-HSL, C6-HSL, 3-oxo-C6-HSL, N-octanoylhomoserine (C8-HSL), determined reduction aqueous solutions time, also less rapid electron-donating longer side chains. Raising temperature from 22 37°C rate opening. Taken together, these data show (i) functional under physiological conditions mammalian tissue fluids, require an least four carbons length (ii) acyl stable molecule.