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

2006 ◽  
Vol 73 (2) ◽  
pp. 535-544 ◽  
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.

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

2009 ◽  
Vol 192 (1) ◽  
pp. 29-37 ◽  
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.

scholarly journals Characterization of a Phosphotriesterase-Like Lactonase fromSulfolobus solfataricusand Its Immobilization for Disruption of Quorum Sensing

2010 ◽  
Vol 77 (4) ◽  
pp. 1181-1186 ◽  
Author(s):  
Filomena S. W. Ng ◽  
Daniel M. Wright ◽  
Stephen Y. K. Seah
Keyword(s):  
Quorum Sensing ◽  
Virulence Factors ◽  
Acyl Chain ◽  
Quorum Quenching ◽  
Homoserine Lactone ◽  
Homoserine Lactones ◽  
Specificity Constant ◽  
Chain Lengths ◽  
Quorum Sensing Signals

ABSTRACTSsoPox, a bifunctional enzyme with organophosphate hydrolase andN-acyl homoserine lactonase activities from the hyperthermophilic archaeonSulfolobus solfataricus, was overexpressed and purified from recombinantPseudomonas putidaKT2440 with a yield of 9.4 mg of protein per liter of culture. The enzyme has a preference forN-acyl homoserine lactones (AHLs) with acyl chain lengths of at least 8 carbon atoms, mainly due to lowerKmvalues for these substrates. The highest specificity constant obtained was forN-3-oxo-decanoyl homoserine lactone (kcat/Km= 5.5 × 103M−1·s−1), but SsoPox can also degradeN-butyryl homoserine lactone (C4-HSL) andN-oxo-dodecanoyl homoserine lactone (oxo-C12-HSL), which are important for quorum sensing in ourPseudomonas aeruginosamodel system. WhenP. aeruginosaPAO1 cultures were grown in the presence of SsoPox-immobilized membranes, the production of C4-HSL- and oxo-C12-HSL-regulated virulence factors, elastase, protease, and pyocyanin were significantly reduced. This is the first demonstration that immobilized quorum-quenching enzymes can be used to attenuate the production of virulence factors controlled by quorum-sensing signals.

scholarly journals LuxS Affects Flagellar Phase Variation Independently of Quorum Sensing in Salmonella enterica Serovar Typhimurium

2007 ◽  
Vol 190 (2) ◽  
pp. 769-771 ◽  
Author(s):  
M. H. Karavolos ◽  
D. M. Bulmer ◽  
K. Winzer ◽  
M. Wilson ◽  
P. Mastroeni ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Phase 1 ◽  
Phase Variation ◽  
Signaling Molecule ◽  
Autoinducer 2 ◽  
Serovar Typhimurium ◽  
Quorum Sensing Signals

ABSTRACT LuxS catalyzes the synthesis of the quorum-sensing signaling molecule autoinducer 2. We show that in Salmonella enterica serovar Typhimurium, deletion of the luxS gene polarizes flagellar phase variation toward the more immunogenic phase 1 flagellin. This phenotype is complementable by luxS in trans but is independent of quorum-sensing signals.

scholarly journals The Acyl Homoserine Lactone Receptor, SdiA, of Escherichia coli and Salmonella enterica Serovar Typhimurium Does Not Respond to Indole

2012 ◽  
Vol 78 (15) ◽  
pp. 5424-5431 ◽  
Author(s):  
Anice Sabag-Daigle ◽  
Jitesh A. Soares ◽  
Jenée N. Smith ◽  
Mohamed E. Elmasry ◽  
Brian M. M. Ahmer
Keyword(s):  
Escherichia Coli ◽  
Salmonella Enterica ◽  
Biofilm Formation ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Homoserine Lactone ◽  
Acyl Homoserine Lactone ◽  
Content Type ◽  
E Coli ◽  
Serovar Typhimurium ◽  
High Concentrations

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.

scholarly journals Quorum Sensing and Production of Autoinducer-2 in Campylobacter spp., Escherichia coli O157:H7, and Salmonella enterica Serovar Typhimurium in Foods

2002 ◽  
Vol 68 (9) ◽  
pp. 4666-4671 ◽  
Author(s):  
Orla M. Cloak ◽  
Barbara T. Solow ◽  
Connie E. Briggs ◽  
Chin-Yi Chen ◽  
Pina M. Fratamico
Keyword(s):  
Escherichia Coli ◽  
Quorum Sensing ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Campylobacter Coli ◽  
Gram Positive Bacteria ◽  
Autoinducer 2 ◽  
Chicken Broth ◽  
Serovar Typhimurium ◽  
Luminescence Assay

ABSTRACT Autoinducer molecules are utilized by gram-negative and gram-positive bacteria to regulate density-dependent gene expression by a mechanism known as quorum sensing. PCR and DNA sequencing results showed that Campylobacter jejuni and Campylobacter coli possessed luxS, which is responsible for autoinducer-2 (AI-2) production. Using a Vibrio harveyi luminescence assay, the production of AI-2 was observed in milk, chicken broth, and brucella broth by C. coli, C. jejuni, Salmonella enterica serovar Typhimurium, and Escherichia coli O157:H7 under different conditions.

scholarly journals Detection of Quorum Sensing Signal Molecules, Particularly N-Acyl Homoserine Lactones, 2-Alky-4-Quinolones, and Diketopiperazines, in Gram-Negative Bacteria Isolated From Insect Vector of Leishmaniasis

2021 ◽  
Vol 2 ◽  
Author(s):  
Rafael Jose Vivero-Gomez ◽  
Gustavo Bedoya Mesa ◽  
Jorge Higuita-Castro ◽  
Sara M. Robledo ◽  
Claudia X. Moreno-Herrera ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Enterobacter Aerogenes ◽  
Enterobacter Cloacae ◽  
Homoserine Lactone ◽  
Migration Pattern ◽  
Insect Vector ◽  
Gram Negative Bacteria ◽  
Homoserine Lactones ◽  
Sensing System ◽  
Intracellular Content

Gram-negative bacteria are known to use a quorum sensing system to facilitate and stimulate cell to cell communication, mediated via regulation of specific genes. This system is further involved in the modulation of cell density and metabolic and physiological processes that putatively either affect the survival of insect vectors or the establishment of pathogens transmitted by them. The process of quorum sensing generally involves N-acyl homoserine lactones and 2-alkyl-4-quinolones signaling molecules. The present study aimed to detect and identify quorum sensing signaling molecules of AHLs and AHQs type that are secreted by intestinal bacteria, and link their production to their extracellular milieu and intracellular content. Isolates for assessment were obtained from the intestinal tract of Pintomyia evansi (Leishmania insect vector). AHLs and AHQs molecules were detected using chromatography (TLC) assays, with the aid of specific and sensitive biosensors. For identity confirmation, ultra-high-performance liquid chromatography coupled with mass spectrometry was used. TLC assays detected quorum sensing molecules (QSM) in the supernatant of the bacterial isolates and intracellular content. Interestingly, Pseudomonas otitidis, Enterobacter aerogenes, Enterobacter cloacae, and Pantoea ananatis isolates showed a migration pattern similar to the synthetic molecule 3-oxo-C6-HSL (OHHL), which was used as a control. Enterobacter cancerogenus secreted C6-HSL, a related molecules to N-hexanoyl homoserine lactone (HHL), while Acinetobacter gyllenbergii exhibited a migration pattern similar to 2-heptyl-4-quinolone (HHQ) molecules. In comparison to this, 3-oxo-C12-HSL (OdDHL) type molecules were produced by Lysobacter soli, Pseudomonas putida, A. gyllenbergii, Acinetobacter calcoaceticus, and Pseudomonas aeruginosa, while Enterobacter cloacae produced molecules similar to 2-heptyl-3-hydroxy-4-quinolone (PQS). For Pseudomonas putida, Enterobacter aerogenes, P. ananatis, and Pseudomonas otitidis extracts, peak chromatograms with distinct retention times and areas, consistent with the molecules described in case of TLC, were obtained using HPLC. Importantly, P. ananatis produced a greater variety of high QSM concentration, and thus served as a reference for confirmation and identification by UHPLC-MRM-MS/MS. The molecules that were identified included N-hexanoyl-L-homoserine lactone [HHL, C10H18NO3, (M + H)], N-(3-oxohexanoyl)-L-homoserine lactone [OHHL, C10H16NO4, (M + H)], N-(3-oxododecanoyl)-L-homoserine lactone [OdDHL, C16H28NO4, (M + H)], and 2-heptyl-3-hydroxy-4(1H)-quinolone [PQS, C16H22NO2, (M + H)]. Besides this, the detection of diketopiperazines, namely L-Pro-L-Tyr and ΔAla-L-Val cyclopeptides was reported for P. ananatis. These molecules might be potentially associated with the regulation of QSM system, and might represent another small molecule-mediated bacterial sensing system. This study presents the first report regarding the detection and identification of QSM and diketopiperazines in the gut sand fly bacteria. The possible effect of QSM on the establishment of Leishmania must be explored to determine its role in the modulation of intestinal microbiome and the life cycle of Pi. evansi.

Sign in / Sign up

Export Citation Format

Share Document