Faculty Opinions recommendation of Salmonella enterica serovar Typhimurium can detect acyl homoserine lactone production by Yersinia enterocolitica in mice.

ABSTRACTIn this study, we tested the hypothesis that the SdiA proteins ofEscherichia coliandSalmonella entericaserovar Typhimurium respond to indole. While indole was found to have effects on gene expression and biofilm formation, these effects were notsdiAdependent. However, high concentrations of indole did inhibitN-acyl-l-homoserine lactone (AHL) sensing by SdiA. We conclude that SdiA does not respond to indole but indole can inhibit SdiA activity inE. coliandSalmonella.

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Salmonella enterica Serovar Typhimurium Can Detect Acyl Homoserine Lactone Production by Yersinia enterocolitica in Mice

Journal of Bacteriology ◽

10.1128/jb.01139-09 ◽

2009 ◽

Vol 192 (1) ◽

pp. 29-37 ◽

Cited By ~ 57

Author(s):

Jessica L. Dyszel ◽

Jenee N. Smith ◽

Darren E. Lucas ◽

Jitesh A. Soares ◽

Matthew C. Swearingen ◽

...

Keyword(s):

Yersinia Enterocolitica ◽

Salmonella Enterica ◽

Salmonella Enterica Serovar Typhimurium ◽

Bacterial Species ◽

Homoserine Lactone ◽

Homoserine Lactones ◽

Fitness Advantage ◽

Acyl Homoserine Lactones ◽

Luxr Homolog ◽

Serovar Typhimurium

ABSTRACT LuxR-type transcription factors detect acyl homoserine lactones (AHLs) and are typically used by bacteria to determine the population density of their own species. Escherichia coli and Salmonella enterica serovar Typhimurium cannot synthesize AHLs but can detect the AHLs produced by other bacterial species using the LuxR homolog, SdiA. Previously we determined that S. Typhimurium did not detect AHLs during transit through the gastrointestinal tract of a guinea pig, a rabbit, a cow, 5 mice, 6 pigs, or 12 chickens. However, SdiA was activated during transit through turtles colonized by Aeromonas hydrophila, leading to the hypothesis that SdiA is used for detecting the AHL production of other pathogens. In this report, we determined that SdiA is activated during the transit of S. Typhimurium through mice infected with the AHL-producing pathogen Yersinia enterocolitica. SdiA is not activated during transit through mice infected with a yenI mutant of Y. enterocolitica that cannot synthesize AHLs. However, activation of SdiA did not confer a fitness advantage in Yersinia-infected mice. We hypothesized that this is due to infrequent or short interactions between S. Typhimurium and Y. enterocolitica or that the SdiA regulon members do not function in mice. To test these hypotheses, we constructed an S. Typhimurium strain that synthesizes AHLs to mimic a constant interaction with Y. enterocolitica. In this background, sdiA + S. Typhimurium rapidly outcompetes the sdiA mutant in mice. All known members of the sdiA regulon are required for this phenotype. Thus, all members of the sdiA regulon are functional in mice.

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Synthesis of N-Acyl Homoserine Lactone Analogues Reveals Strong Activators of SdiA, the Salmonella enterica Serovar Typhimurium LuxR Homologue

Applied and Environmental Microbiology ◽

10.1128/aem.01451-06 ◽

2006 ◽

Vol 73 (2) ◽

pp. 535-544 ◽

Cited By ~ 41

Author(s):

Joost C. A. Janssens ◽

Kristine Metzger ◽

Ruth Daniels ◽

Dave Ptacek ◽

Tine Verhoeven ◽

...

Keyword(s):

Quorum Sensing ◽

Salmonella Enterica ◽

Salmonella Enterica Serovar Typhimurium ◽

Vibrio Fischeri ◽

Acyl Chain ◽

Homoserine Lactone ◽

Gram Negative Bacteria ◽

Ligand Interaction ◽

Homoserine Lactones ◽

Serovar Typhimurium

ABSTRACT N-Acyl homoserine lactones (AHLs) are molecules that are synthesized and detected by many gram-negative bacteria to monitor the population density, a phenomenon known as quorum sensing. Salmonella enterica serovar Typhimurium is an exceptional species since it does not synthesize its own AHLs, while it does encode a LuxR homologue, SdiA, which enables this bacterium to detect AHLs that are produced by other species. To obtain more information about the specificity of the ligand binding by SdiA, we synthesized and screened a limited library of AHL analogues. We identified two classes of analogues that are strong activators of SdiA: the N-(3-oxo-acyl)-homocysteine thiolactones (3O-AHTLs) and the N-(3-oxo-acyl)-trans-2-aminocyclohexanols. To our knowledge, this is the first report of compounds (the 3O-AHTLs) that are able to activate a LuxR homologue at concentrations that are lower than the concentrations of the most active AHLs. SdiA responds with greatest sensitivity to AHTLs that have a keto modification at the third carbon atom and an acyl chain that is seven or eight carbon atoms long. The N-(3-oxo-acyl)-trans-2-aminocyclohexanols were found to be less sensitive to deactivation by lactonase and alkaline pH than the 3O-AHTLs and the AHLs are. We also examined the activity of our library with LuxR of Vibrio fischeri and identified three new inhibitors of LuxR. Finally, we performed preliminary binding experiments which suggested that SdiA binds its activators reversibly. These results increase our understanding of the specificity of the SdiA-ligand interaction, which could have uses in the development of anti-quorum-sensing-based antimicrobials.

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pfs-Dependent Regulation of Autoinducer 2 Production in Salmonella enterica Serovar Typhimurium

Journal of Bacteriology ◽

10.1128/jb.184.13.3450-3456.2002 ◽

2002 ◽

Vol 184 (13) ◽

pp. 3450-3456 ◽

Cited By ~ 83

Author(s):

Anne L. Beeston ◽

Michael G. Surette

Keyword(s):

Gene Product ◽

Salmonella Enterica ◽

Salmonella Enterica Serovar Typhimurium ◽

Regulation Of Gene Expression ◽

Carbon Sources ◽

Homoserine Lactone ◽

Bacterial Cells ◽

Autoinducer 2 ◽

Serovar Typhimurium ◽

Signal Synthesis

ABSTRACT Bacterial intercellular communication provides a mechanism for signal-dependent regulation of gene expression to promote coordinated population behavior. Salmonella enterica serovar Typhimurium produces a non-homoserine lactone autoinducer in exponential phase as detected by a Vibrio harveyi reporter assay for autoinducer 2 (AI-2) (M. G. Surette and B. L. Bassler, Proc. Natl. Acad. Sci. USA 95:7046-7050, 1998). The luxS gene product mediates the production of AI-2 (M. G. Surette, M. B. Miller, and B. L. Bassler, Proc. Natl. Acad. Sci. USA 96:1639-1644, 1999). Environmental cues such as rapid growth, the presence of preferred carbon sources, low pH, and/or high osmolarity were found to influence the production of AI-2 (M. G. Surette and B. L. Bassler, Mol. Microbiol. 31:585-595, 1999). In addition to LuxS, the pfs gene product (Pfs) is required for AI-2 production, as well as S-adenosylhomocysteine (SAH) (S. Schauder, K. Shokat, M. G. Surette, and B. L. Bassler, Mol. Microbiol. 41:463-476, 2001). In bacterial cells, Pfs exhibits both 5′-methylthioadenosine (MTA) and SAH nucleosidase functions. Pfs is involved in methionine metabolism, regulating intracellular MTA and SAH levels (elevated levels of MTA and SAH are potent inhibitors of polyamine synthetases and S-adenosylmethionine dependent methyltransferase reactions, respectively). To further investigate regulation of AI-2 production in Salmonella, we constructed pfs and luxS promoter fusions to a luxCDABE reporter in a low-copy-number vector, allowing an examination of transcription of the genes in the pathway for signal synthesis. Here we report that luxS expression is constitutive but that the transcription of pfs is tightly correlated to AI-2 production in Salmonella serovar Typhimurium 14028. Neither luxS nor pfs expression appears to be regulated by AI-2. These results suggest that AI-2 production is regulated at the level of LuxS substrate availability and not at the level of luxS expression. Our results indicate that AI-2-dependent signaling is a reflection of metabolic state of the cell and not cell density.

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