pfs-Dependent Regulation of Autoinducer 2 Production inSalmonella entericaSerovar Typhimurium

Beeston, Anne; Surette, Michael G.

doi:10.1128/jb.184.13.3450-3456.2002

Cited by 101 publications

(103 citation statements)

References 43 publications

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“…It was originally proposed that the acyl-HSL signal senses an individual species' cell density, whereas the nonspecific AI-2 senses the cumulative cell density of the bacterial community (1). The discovery that AI-2 signal production is dependent on the growth conditions rather than cell density per se has led to the alternative hypothesis that AI-2 reflects a change in environmental conditions through a change in the metabolic activity of the bacterial community (4,43). These findings, together with the fact that LuxS has a role in central metabolism, led to the proposal that in most bacteria AI-2 is not a specific signal but a metabolic by-product of a common detoxifying pathway (49).…”

Section: Discussionmentioning

confidence: 99%

Vibrio fischeri LuxS and AinS: Comparative Study of Two Signal Synthases

2004

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Vibrio fischeri possesses two acyl-homoserine lactone quorum-sensing systems, ain and lux, both of which are involved in the regulation of luminescence gene expression and are required for persistent colonization of the squid host, Euprymna scolopes. We have previously demonstrated that the ain system induces luminescence at cell densities that precede lux system activation. Our data suggested that the ain system both relieves repression and initially induces the lux system, thereby achieving sequential induction of gene expression by these two systems. Analysis of the V. fischeri genome revealed the presence of a putative third system based on the enzyme LuxS, which catalyzes the synthesis of the Vibrio harveyi autoinducer 2 (AI-2). In this study, we investigated the impact of V. fischeri LuxS on luminescence and colonization competence in comparison to that of the ain system. Similar to the ain system, inactivation of the AI-2 system decreased light production in culture, but not in the squid host. However, while an ainS mutant produces no detectable light in culture, a luxS mutant expressed approximately 70% of wild-type luminescence levels. A mutation in luxS alone did not compromise symbiotic competence of V. fischeri; however, levels of colonization of an ainS luxS double mutant were reduced to 50% of the already diminished level of ainS mutant colonization, suggesting that these two systems regulate colonization gene expression synergistically through a common pathway. Introduction of a luxO mutation into the luxS and ainS luxS background could relieve both luminescence and colonization defects, consistent with a model in which LuxS, like AinS, regulates gene expression through LuxO. Furthermore, while luxS transcription appeared to be constitutive and the AI-2 signal concentration did not change dramatically, our data suggest that ainS transcription is autoregulated, resulting in an over 2,000-fold increase in signal concentration as culture density increased. Taken together, these data indicate that V. fischeri LuxS affects both luminescence regulation and colonization competence; however, its quantitative contribution is small when compared to that of the AinS signal.Vibrio fischeri, the bacterial light organ symbiont of the Hawaiian squid Euprymna scolopes, utilizes at least two quorumsensing systems whose relative importance is dependent on cell density: (i) the well-known lux system, consisting of LuxI, which synthesizes N-(3-oxo-hexanoyl) homoserine lactone (3-oxo-C6-HSL), and the transcriptional regulator LuxR (14); and (ii) the ain system, which includes the second V. fischeri acyl-HSL synthase AinS, generating N-octanoyl HSL (C8-HSL) (16,23,24). We have previously demonstrated that these two systems are important at different cell densities: i.e., the ain system is the predominant inducer of luminescence in culture (24), whereas the lux system is necessary for luminescence expression at the higher cell densities present in the squid light organ (44). This sequential induction of luminescence gen...

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Section: Discussionmentioning

confidence: 99%

Vibrio fischeri LuxS and AinS: Comparative Study of Two Signal Synthases

2004

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“…It is likely, therefore, that production of DPD is directly correlated with cellular fitness, and, reciprocally, that DPD may function as a signal of bacterial fitness (Xavier & Bassler, 2003). Such a signal may function extracellularly, to influence the entire population, intracellularly as an alarmone to modify expression levels of that bacterium's own genes, or as a combination of these two possibilities (Beeston & Surette, 2002;Camilli & Bassler, 2006;Redfield, 2002;Xavier & Bassler, 2003).…”

Section: Discussionmentioning

confidence: 99%

Genetic and physiological characterization of the Borrelia burgdorferi ORF BB0374-pfs-metK-luxS operon

et al. 2007

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The Lyme disease spirochaete, Borrelia burgdorferi, produces the LuxS enzyme both in vivo and in vitro; this enzyme catalyses the synthesis of homocysteine and 4,5-dihydroxy-2,3-pentanedione (DPD) from a by-product of methylation reactions. Unlike most bacteria, B. burgdorferi is unable to utilize homocysteine. However, DPD levels alter expression levels of a subset of B. burgdorferi proteins. The present studies demonstrate that a single B. burgdorferi operon encodes both of the enzymes responsible for synthesis of DPD, as well as the enzyme for production of the Lyme spirochaete's only activated-methyl donor and a probable phosphohydrolase. Evidence was found for only a single transcriptional promoter, located 59 of the first gene, which uses the housekeeping s 70 subunit for RNA polymerase holoenzyme function. All four genes are co-expressed, and mRNA levels are growth-rate dependent, being produced during the exponential phase. Thus, high metabolic activity is accompanied by increased cellular levels of the only known borrelial methyl donor, enhanced detoxification of methylation by-products, and increased production of DPD. Therefore, production of DPD is directly correlated with cellular metabolism levels, and may thereby function as an extracellular and/or intracellular signal of bacterial health. INTRODUCTIONLyme disease is an arthropod-borne zoonotic disease affecting humans and many domesticated and wild animals. The causative agent, Borrelia burgdorferi, is readily able to infect both Ixodes spp. ticks and a variety of vertebrate hosts (Steere, 2001). Throughout the processes of infecting these two distinct host types, and transmission between each, B. burgdorferi regulates expression of a large number of both metabolic and host-interface proteins. Deciphering the mechanisms by which B. burgdorferi controls gene and protein expression patterns is providing insights into both the physiology of this bacterium and its pathogenic abilities.Some species of bacteria utilize the metabolic by-product 4,5-dihydroxy-2,3-pentanedione (DPD) in intercellular (and possibly intracellular) signalling. Several different, spontaneously derived forms of DPD have been identified that can function as signals, which are collectively termed 'autoinducer-2' (AI-2) (Chen et al., 2002;Miller et al., 2004). DPD/AI-2 is produced from the toxic end product of transmethylation reactions, S-adenosylhomocysteine (SAH), in a two-step reaction catalysed by the enzymes Pfs and LuxS. Some bacteria, such as the syphilis spirochaete Treponema pallidum, possess Pfs but lack LuxS, and therefore detoxify SAH only to the non-toxic S-ribosylhomocysteine (SRH) (Fraser et al., 1998;von Lackum et al., 2006). Other bacteria, B. burgdorferi included, further degrade SRH to DPD and homocysteine via the LuxS enzyme (Babb et al., 2005;Stevenson & Babb, 2002;Stevenson et al., 2003;Sun et al., 2004;Xavier & Bassler, 2003). The majority of bacteria salvage homocysteine for regeneration of methionine, for use in additional transmethylation reactions or pr...

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“…Indeed, studies in the Gram-positive Streptococcus gordoni have allowed the proposal that AI-2 production is regulated at the metabolic level (Blehert et al, 2003). In Salmonella enterica serovar Typhimurium, AI-2 production depends on the level of LuxS substrate availability, rather than luxS expression, and reflects the metabolic state of the cell (Beeston & Surette, 2002). In S. pneumoniae, LuxS may contribute to the amplification of cellular metabolic signals to the whole population via the production of molecules allowing cell-cell communication.…”

Section: Competence Developmentmentioning

confidence: 99%

LuxS impacts on LytA-dependent autolysis and on competence in Streptococcus pneumoniae

et al. 2006

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The ubiquitous protein LuxS with S-ribosylhomocysteinase activity is involved in S-adenosyl methionine detoxification, C-1 unit recycling and the production of autoinducers that allow the cell to sense and respond to cell density. Independent reports describe the impact of LuxS deficiency on Streptococcus pneumoniae virulence in the mouse. In vitro, LuxS deficiency confers discrete phenotypes. A combined approach using genetic dissection and mixed-culture experiments allowed the involvement of LuxS in the developmental physiology of S. pneumoniae to be investigated. Functional LuxS was found to be related on the one hand to down-regulation of competence, and on the other hand to attenuation of autolysis in cultures entering stationary phase. The competence phenotype of luxS mutant bacteria was complemented by media conditioned by competence-defective ComAB0 bacteria, but not by BSA. The autolytic phenotype was complemented by BSA, but not by conditioned supernatants. It is suggested that the impact of LuxS on competence, but not on autolysis, involves cell-cell communication. The phenotype of luxS mutant strains reveals a hierarchy in the competence regulatory networks of S. pneumoniae. INTRODUCTIONLuxS, the S-ribosylhomocysteinase involved in furanosyl borate diester, autoinducer 2 (AI-2) production from Sribosylhomocysteine, is ubiquitous in prokaryotes (Sun et al., 2004). Since its discovery (Bassler et al., 1997) and chemical characterization (Chen et al., 2002), the role of AI-2 in the regulation of light production, biofilm formation and virulence in response to high cell density (quorum sensing) has been elucidated in several Gram-negative bacteria, including Vibrio species (Surette et al., 1999;Miller et al., 2002;Hammer & Bassler, 2003;Henke & Bassler, 2004;Vendeville et al., 2005). In some species, furanone uptake and processing involving the lsrACDBFGE operon has been described Xavier & Bassler, 2005). Bioluminescence activation in Vibrio harveyi by conditioned media represents the test for AI-2 production by a given species and supports the paradigm of AI-2-mediated interspecies cell-cell communication culminating in genetic regulation Xavier & Bassler, 2003). Recent studies give credence to the involvement of LuxS in host-bacterial communication (Maroui & Sela, 2003;Sperandino et al., 2003). However, in Neisseria meningitis, AI-2 production is not related to the regulation of specific genes in vitro (Schauder et al., 2005;Dove et al., 2003). In Streptococcus pneumoniae, the impact of LuxS loss-offunction mutations on experimental virulence and genetic expression has been reported; however, results concerning production of AI-2, active in the 'vibrio test', by pneumococci, are divergent (Joyce et al. 2004;Stroeher et al., 2003). In order to get further insight into the function of LuxS in these Gram-positive bacteria, we have investigated its role in vitro on the developmental phenotypes classically observed: competence for genetic transformation during exponential growth, and autolysis when the cult...

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pfs-Dependent Regulation of Autoinducer 2 Production inSalmonella entericaSerovar Typhimurium

Cited by 101 publications

References 43 publications

Vibrio fischeri LuxS and AinS: Comparative Study of Two Signal Synthases

Vibrio fischeri LuxS and AinS: Comparative Study of Two Signal Synthases

Genetic and physiological characterization of the Borrelia burgdorferi ORF BB0374-pfs-metK-luxS operon

LuxS impacts on LytA-dependent autolysis and on competence in Streptococcus pneumoniae

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