Role of<i>Neisseria meningitidis luxS</i>in Cell-to-Cell Signaling and Bacteremic Infection

Winzer, Klaus; Sun, Yaohui; Green, Andrew; Delory, Marie; Blackley, David J.; Hardie, Kim R.; Baldwin, Thomas J.; Tang, Christoph M.

doi:10.1128/iai.70.4.2245-2248.2002

Cited by 70 publications

(74 citation statements)

References 29 publications

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“…Using this model, we showed that the S. marcescens 274 luxS mutant exhibits a subtle but reproducible virulence defect. Attenuation of virulence has been seen in various luxS mutants, for example in N. meningitidis, V. vulnificus and Streptococcus pneumoniae; although in other bacteria, virulence is not significantly altered in the luxS mutant, at least in the chosen model (Burgess et al, 2002;Kim et al, 2003;Schneider et al, 2002;Stroeher et al, 2003;Winzer et al, 2002b). The reduced production of haemolysin and/or prodigiosin by the luxS mutant of S. marcescens 274 may contribute to its altered virulence.…”

Section: Discussionmentioning

confidence: 99%

“…in Helicobacter pylori and Proteus mirabilis), through to altered production of virulence determinants (e.g. in Porphyromonas gingivalis, Streptococcus pyogenes and Clostridium perfringens), and decreased virulence (in Neisseria meningitidis, Streptococcus pneumoniae and Vibrio vulnificus) (Burgess et al, 2002;Joyce et al, 2000;Kim et al, 2003;Lyon et al, 2001;Ohtani et al, 2002;Schneider et al, 2002;Stroeher et al, 2003;Winzer et al, 2002b). However, the elucidation of the biosynthetic pathway of AI-2 has revealed a metabolic role for LuxS, in the S-adenosylmethionineutilization pathway (Schauder et al, 2001;Winzer et al, 2002a).…”

Section: Introductionmentioning

confidence: 99%

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luxS mutants of Serratia defective in autoinducer-2-dependent ‘quorum sensing’ show strain-dependent impacts on virulence and production of carbapenem and prodigiosin

2004

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The enzyme LuxS is responsible for the production of autoinducer-2 (AI-2), a molecule that has been implicated in quorum sensing in many bacterial species. This study investigated whether there is a luxS-dependent signalling system in the Gram-negative bacteria Serratia spp. Serratia marcescens is a broad-host-range pathogen and an important cause of nosocomial infections. Production of AI-2 activity was detected in S. marcescens ATCC 274 and Serratia ATCC 39006 and their luxS genes were sequenced. luxS mutants were constructed in these strains and were analysed to determine which phenotypes are regulated by luxS and therefore, potentially, by AI-2. The phenotypes of the luxS mutants included decreased carbapenem antibiotic production in Serratia ATCC 39006 and decreased prodigiosin and secreted haemolysin production in S. marcescens ATCC 274. The luxS mutant of S. marcescens ATCC 274 was also found to exhibit modestly reduced virulence in a Caenorhabditis elegans model. Finally, it was shown that the culture supernatant of a wild-type strain contains a signal, presumably AI-2, capable of complementing the prodigiosin defect of the luxS mutant of another strain, even when substantially diluted. It is concluded that luxS modulates virulence and antibiotic production in Serratia, in a strain-dependent manner, and that, for at least one phenotype, this regulation is via extracellular signalling.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

luxS mutants of Serratia defective in autoinducer-2-dependent ‘quorum sensing’ show strain-dependent impacts on virulence and production of carbapenem and prodigiosin

2004

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“…typhimurium, Sh. flexneri and Strep. pyogenes (Sperandio et al, 1999 ;Forsyth & Cover, 2000 ;Joyce et al, 2000 ;Burgess et al, 2002 ;Day & Maurelli, 2001 ;Lyon et al, 2001 ;Winzer et al, 2002). Although a DNA-microarray-based approach suggested that several hundred genes were up-or down-regulated in an E. coli O157 : H7 luxS mutant (Spernandio et al, 2001), these changes have not yet been linked to a lack of AI-2 activity, and may in fact be explained by additional functions of the luxS gene product.…”

Section: Introductionmentioning

confidence: 99%

“…In Vibrio harveyi, the LuxS protein is required for the production of a signal molecule of unknown structure, autoinducer 2 (AI-2), which exerts its activity via a complex phospho-relay system. AI-2 activity has been discovered in spent culture supernatants of many organisms, including Escherichia coli, Helicobacter pylori, Neisseria meningitidis, Porphyromonas gingivalis, Streptococcus pyogenes, Shigella flexneri and Salmonella typhimurium (Bassler et al, 1997 ;Surette & Bassler, 1998 ;Sperandio et al, 1999 ;Forsyth & Cover, 2000 ;Joyce et al, 2000 ;Burgess et al, 2002 ;Day & Maurelli, 2001 ;Lyon et al, 2001 ;Winzer et al, 2002). Furthermore, highly conserved LuxS homologues have been identified in a large number of pathogenic and nonpathogenic bacteria by database analysis Bassler, 1999).…”

Section: Introductionmentioning

confidence: 99%

LuxS: its role in central metabolism and the in vitro synthesis of 4-hydroxy-5-methyl-3(2H)-furanone

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Many bacteria produce extracellular molecules which function in cell-to-cell communication. One of these molecules, autoinducer 2 (AI-2), was first described as an extracellular signal produced by Vibrio harveyi to control luciferase expression. Subsequently, a number of bacteria have been shown to possess AI-2 activity in their culture supernatants, and bear the luxS gene product, which is required for AI-2 synthesis. In Porphyromonas gingivalis, luxS and pfs, encoding a 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTA/SAH'ase), form an operon, suggesting that Sadenosylhomocysteine (SAH) or 5'-methylthioadenosine (MTA) serves as a substrate for AI-2 production. Cell-free extracts of Escherichia coli MG1655, but not DH5α (which carries a luxS frame-shift mutation) were capable of generating AI-2 activity upon addition of SAH, but not MTA. S-Ribosylhomocysteine (RH) derived from SAH also served as a substrate in E. coli MG1655 extracts. RH-supplemented cell-free extracts of Pseudomonas aeruginosa, a bacterium that lacks luxS, only generated AI-2 activity following the introduction of a plasmid containing the Por. gingivalis pfs-luxS operon. In addition, defined in vitro systems consisting of the purified LuxS proteins from Por. gingivalis, E. coli, Neisseria meningitidis or Staphylococcus aureus converted RH to homocysteine and a compound that exhibits AI-2 activity. 4-Hydroxy-5-methyl-3(2H)-furanone was identified by mass spectrometry analysis as a major product formed in this in vitro reaction. In E. coli MG1655, expression of T3SH [the bacteriophage T3 S-adenosylmethionine (SAM) hydrolase] significantly reduced AI-2 activity in culture supernatants, suggesting that AI-2 production is limited by the amount of SAH produced in SAM-dependent transmethylase reactions. The authors suggest that the LuxS protein has an important metabolic function in the recycling of SAH. They also show that Ps. aeruginosa is capable of removing AI-2 activity, implying that this molecule may act as a nutrient. In many bacteria AI-2 may in fact represent not a signal molecule but a metabolite which is released early and metabolized in the later stages of growth.

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“…Consistent with its proposed role as an interspecies communication signal, AI-2-mediated signal transduction circuits have been found to regulate biological processes that coordinate the behaviour of cells as a community to best adapt to various environmental situations. Such biological processes include biofilm formation, conjugation, sporulation, and production of virulence elements (Gonzalez Barrios et al, 2006;McNab et al, 2003;Rickard et al, 2006;; the last has been linked to the LuxS/AI-2 quorumsensing system via, most often, mutational studies of the luxS gene (Lyon et al, 2001;Marouni & Sela, 2003;Ohtani et al, 2002;Stroeher et al, 2003;Winzer et al, 2002b;Zhu et al, 2002). been reported to occur in different parts of the world.…”

Section: Introductionmentioning

confidence: 99%

Regulation of autoinducer 2 production and luxS expression in a pathogenic Edwardsiella tarda strain

2008

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Edwardsiella tarda is a bacterial pathogen that can infect both humans and animals. TX1, an Ed. tarda strain isolated from diseased fish, was found to produce autoinducer 2 (AI-2)-like activity that was growth phase dependent and modulated by growth conditions. The gene coding for the AI-2 synthase was cloned from TX1 and designated luxS Et. LuxS Et was able to complement the AI-2 mutant phenotype of Escherichia coli strain DH5a. Expression of luxS Et correlated with AI-2 activity and was increased by glucose and decreased by elevated temperature. The effect of glucose was shown to be mediated through the cAMP-CRP complex, which repressed luxS Et expression. Overexpression of luxS Et enhanced AI-2 activity in TX1, whereas disruption of luxS Et expression by antisense RNA interference (i) reduced the level of AI-2 activity, (ii) impaired bacterial growth under various conditions, (iii) weakened the expression of genes associated with the type III secretion system and biofilm formation, and (iv) attenuated bacterial virulence. Addition of exogenous AI-2 was able to complement the deficiencies in the expression of TTSS genes and biofilm production but failed to rescue the growth defects. Our results (i) demonstrated that the AI-2 activity in TX1 is controlled at least in part at the level of luxS Et expression, which in turn is regulated by growth conditions, and that the temporal expression of luxS Et is essential for optimal bacterial infection and survival; and (ii) suggested the existence in Ed. tarda of a LuxS/AI-2-mediated signal transduction pathway that regulates the production of virulence-associated elements.

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Role ofNeisseria meningitidis luxSin Cell-to-Cell Signaling and Bacteremic Infection

Cited by 70 publications

References 29 publications

luxS mutants of Serratia defective in autoinducer-2-dependent ‘quorum sensing’ show strain-dependent impacts on virulence and production of carbapenem and prodigiosin

luxS mutants of Serratia defective in autoinducer-2-dependent ‘quorum sensing’ show strain-dependent impacts on virulence and production of carbapenem and prodigiosin

LuxS: its role in central metabolism and the in vitro synthesis of 4-hydroxy-5-methyl-3(2H)-furanone

Regulation of autoinducer 2 production and luxS expression in a pathogenic Edwardsiella tarda strain

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