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 the cell population density-dependent control of genes associated with virulence. This phenomenon, termed quorum sensing, relies upon the accumulation of AHLs to a threshold concentration at which target structural genes are activated. By using biosensors capable of detecting a range of AHLs we observed that, in cultures of Y. pseudotuberculosis and P. aeruginosa, AHLs accumulate during the exponential phase but largely disappear during the stationary phase. When added to late-stationary-phase, cell-free culture supernatants of the respective pathogen, the major P. aeruginosa [N-butanoylhomoserine lactone (C4-HSL) and N-(3-oxododecanoyl)homoserine lactone (3-oxo-C12-HSL)] and Y. pseudotuberculosis [N-(3-oxohexanoyl)homoserine lactone (3-oxo-C6-HSL) and N-hexanoylhomoserine lactone (C6-HSL)] AHLs were inactivated. Short-acyl-chain compounds (e.g., C4-HSL) were turned over more extensively than long-chain molecules (e.g., 3-oxo-C12-HSL). Little AHL inactivation occurred with cell extracts, and no evidence for inactivation by specific enzymes was apparent. This AHL turnover was discovered to be due to pH-dependent lactonolysis. By acidifying the growth media to pH 2.0, lactonolysis could be reversed. By using carbon-13 nuclear magnetic resonance spectroscopy, we found that the ring opening of homoserine lactone (HSL), N-propionyl HSL (C3-HSL), and C4-HSL increased as pH increased but diminished as the N-acyl chain was lengthened. At low pH levels, the lactone rings closed but not via a simple reversal of the ring opening reaction mechanism. Ring opening of C4-HSL, C6-HSL, 3-oxo-C6-HSL, and N-octanoylhomoserine lactone (C8-HSL), as determined by the reduction of pH in aqueous solutions with time, was also less rapid for AHLs with more electron-donating longer side chains. Raising the temperature from 22 to 37°C increased the rate of ring opening. Taken together, these data show that (i) to be functional under physiological conditions in mammalian tissue fluids, AHLs require an N-acyl side chain of at least four carbons in length and (ii) that the longer the acyl side chain the more stable the AHL signal molecule.Many gram-negative bacteria regulate gene expression in a cell-density-dependent manner by using N-acyl homoserine lactone (AHL) quorum-sensing signal molecules. AHLs diffuse into and out of bacterial cells and, as the population of bacteria increases, so does the AHL concentration. Once the AHLs reach a threshold concentration, they act as coinducers, usually by activating LuxR-type transcriptional regulators to induce target gene expression. AHL-dependent quorum sensing is known to regulate many different physiological processes, including the production of secondary metabolites, swimming, swarming, biofilm maturation, and virulence in human, plant, and animal pathogens (for reviews, see references 43 and 47)....

Quorum sensing (QS) refers to the capacity of bacteria to monitor their population density and regulate gene expression accordingly: the QS-regulated processes deal with multicellular behaviors (e.g. growth and development of biofilm), horizontal gene transfer and host-microbe (symbiosis and pathogenesis) and microbe-microbe interactions. QS signaling requires the synthesis, exchange and perception of bacterial compounds, called autoinducers or QS signals (e.g. N-acylhomoserine lactones). The disruption of QS signaling, also termed quorum quenching (QQ), encompasses very diverse phenomena and mechanisms which are presented and discussed in this review. First, we surveyed the QS-signal diversity and QS-associated responses for a better understanding of the targets of the QQ phenomena that organisms have naturally evolved and are currently actively investigated in applied perspectives. Next the mechanisms, targets and molecular actors associated with QS interference are presented, with a special emphasis on the description of natural QQ enzymes and chemicals acting as QS inhibitors. Selected QQ paradigms are detailed to exemplify the mechanisms and biological roles of QS inhibition in microbe-microbe and host-microbe interactions. Finally, some QQ strategies are presented as promising tools in different fields such as medicine, aquaculture, crop production and anti-biofouling area.