A B C 3 - oxo - C 6 - HSL C 6 - HSL C 7 - HSL C 8 - HSL C 5 - HSL

Bacterial cell-to-cell communication (‘quorum sensing’) is mediated by structurally diverse, small diffusible signal molecules which regulate gene expression as a function of cell population density. Many different Gramnegative animal, plant and fish pathogens employ Nacylhomoserine lactones (AHLs) as quorum sensing signal molecules which control diverse physiological processes including bioluminescence, swarming, antibiotic biosynthesis, plasmid conjugal transfer, biofilm development and virulence. AHL-dependent quorum sensing is highly conserved in both pathogenic and nonpathogenic members of the genus Yersinia. Yersinia pseudotuberculosis for example, produces at least eight different AHLs and possesses two homologues of the LuxI family of AHL synthases and two members of the LuxR family of AHL-dependent response regulators. In all Yersinia species so far examined, the genes coding for LuxR and LuxI homologues are characteristically arranged convergently and overlapping. In Y. pseudotuberculosis AHL-dependent quorum sensing is involved in the control of cell aggregation and swimming motility, the latter via the flagellar regulatory cascade. This is also the case for swimming and also swarming motility in Yersinia enterocolitica. However the role of AHL-dependent quorum sensing in Yersinia pestis remains to be determined. Introduction Until relatively recently, cell-to-cell communication was rarely considered to constitute a major mechanism for facilitating bacterial adaptation to an environmental challenge. However, it is now clear that diverse bacterial genera communicate using specific, extracellular signal molecules, which facilitate the coordination of gene expression in a multi-cellular fashion. Signalling can be linked to specific environmental or physiological conditions and is employed by bacteria to monitor their cell population density. The term quorum sensing is commonly used to describe the phenomenon whereby the accumulation of a diffusible, low molecular weight signal molecule (sometimes called an ‘autoinducer’) enables individual bacterial cells to sense when the minimum number or quorum of bacteria has been achieved for a concerted response to be initiated (Williams et al., 2000; Swift et al., 2001; Cámara et al., 2002). The term ‘autoinducer’, implies a positive feedback or autoregulatory mechanism of action. However this is frequently not the case and therefore the term can be misleading and will be avoided here (Cámara et al., 2002). The accumulation of a diffusible signal molecule also indicates the presence of a diffusion barrier, which ensures that more molecules are produced than lost from the micro-habitat (Winzer et al., 2002b; Redfield, 2002). This could be regarded as a type of ‘compartment sensing’, where signal molecule accumulation is both the measure for the degree of compartmentalization and the means to distribute this information among the entire population. Similarly, diffusion of quorum sensing signal molecules between spatially separated bacterial sub-populations may convey information about their physiological state, their numbers, and the individual environmental conditions encountered. At the molecular level, quorum sensing requires a synthase together with a signal transduction system for producing and responding to the signal molecule respectively. The latter usually involves a response regulator and/or sensor kinase protein (Swift et al., 2001; Cámara et al., 2002). While quorum sensing systems are ubiquitous in both Gram-negative and Gram-positive bacteria, there is considerable chemical diversity in the nature of the signal molecules involved which range from post-translationally modified peptides to quinolones, lactones and furanones (Cámara et al., 2002). In addition, siderophores, which previously were considered only in the context of iron transport, may also function in the producer organism as signal molecules capable of controlling genes unrelated to iron acquisition (Lamont et al., 2002). While there is, as yet, no clear cut evidence for a molecularly conserved quorum sensing system throughout the bacterial kingdom, the LuxS protein and the furanone generated from the ribosyl moiety of Sribosylhomocysteine (termed AI-2 for autoinducer-2) have been suggested to fulfil such a role (Bassler, 2002). However, many bacteria (e.g. the pseudomonads) do not possess luxS and hence do not produce AI-2 (Winzer et al., 2002a). Furthermore, as LuxS is a key metabolic enzyme in the activated methyl cycle responsible for recycling S-adenosylmethionine (SAM) (Winzer et al., 2002b; Winzer et al., 2002a) phenotypes associated with mutation of luxS are often not a consequence of a defect in cell-to-cell communication but the result of the failure to recycle SAM metabolites (Winzer et al., 2002b; Winzer et al., 2002a). To date, only in Vibrio harveyi is there any direct experimental data to support the function of LuxS as a quorum sensing signal molecule synthase. Thus although Yersinia spp. possess a luxS gene and produce AI-2 (unpublished data) this does not constitute evidence for the presence of a quorum sensing system based on AI-2. Here we examine the nature and contribution of Nacylhomoserine lactone (AHL)-mediated quorum sensing to the lifestyle of Yersinia spp. Quorum Sensing and the Lifestyle of Yersinia