The Experts below are selected from a list of 1212 Experts worldwide ranked by ideXlab platform
Karina B. Xavier - One of the best experts on this subject based on the ideXlab platform.
-
AI-2-mediated signalling in bacteria
FEMS Microbiology Reviews, 2013Co-Authors: Catarina S. Pereira, Jessica A Thompson, Karina B. XavierAbstract:Success in nature depends upon an ability to perceive and adapt to the surrounding environment. Bacteria are not an exception; they recognize and constantly adjust to changing situations by sensing environmental and self-produced signals, altering gene expression accordingly. Autoinducer-2 (AI-2) is a signal molecule produced by LuxS, an enzyme found in many bacterial species and thus proposed to enable Interspecies Communication. Two classes of AI-2 receptors and many layers and interactions involved in downstream signalling have been identified so far. Although AI-2 has been implicated in the regulation of numerous niche-specific behaviours across the bacterial kingdom, interpretation of these results is complicated by the dual role of LuxS in signalling and the activated methyl cycle, a crucial central metabolic pathway. In this article, we present a comprehensive review of the discovery and early characterization of AI-2, current developments in signal detection, transduction and regulation, and the major studies investigating the phenotypes regulated by this molecule. The development of novel tools should help to resolve many of the remaining questions in the field; we highlight how these advances might be exploited in AI-2 quorum quenching, treatment of diseases, and the manipulation of beneficial behaviours caused by polyspecies communities.
-
processing the Interspecies quorum sensing signal autoinducer 2 ai 2 characterization of phospho s 4 5 dihydroxy 2 3 pentanedione isomerization by lsrg protein
Journal of Biological Chemistry, 2011Co-Authors: Joao C Marques, Stephen T. Miller, M F Semmelhack, Pedro Lamosa, Caitlin Russell, Rita Ventura, Christopher D Maycock, Karina B. XavierAbstract:The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is the precursor of the signal molecule autoinducer-2 (AI-2). AI-2 mediates Interspecies Communication and facilitates regulation of bacterial behaviors such as biofilm formation and virulence. A variety of bacterial species have the ability to sequester and process the AI-2 present in their environment, thereby interfering with the cell-cell Communication of other bacteria. This process involves the AI-2-regulated lsr operon, comprised of the Lsr transport system that facilitates uptake of the signal, a kinase that phosphorylates the signal to phospho-DPD (P-DPD), and enzymes (like LsrG) that are responsible for processing the phosphorylated signal. Because P-DPD is the intracellular inducer of the lsr operon, enzymes involved in P-DPD processing impact the levels of Lsr expression. Here we show that LsrG catalyzes isomerization of P-DPD into 3,4,4-trihydroxy-2-pentanone-5-phosphate. We present the crystal structure of LsrG, identify potential catalytic residues, and determine which of these residues affects P-DPD processing in vivo and in vitro. We also show that an lsrG deletion mutant accumulates at least 10 times more P-DPD than wild type cells. Consistent with this result, we find that the lsrG mutant has increased expression of the lsr operon and an altered profile of AI-2 accumulation and removal. Understanding of the biochemical mechanisms employed by bacteria to quench signaling of other species can be of great utility in the development of therapies to control bacterial behavior.
-
Identification of functional LsrB-like autoinducer-2 receptors.
Journal of Bacteriology, 2009Co-Authors: C Pereira, Patricia H Brito, Anna K. De Regt, Stephen T. Miller, Karina B. XavierAbstract:Although a variety of bacterial species have been reported to use the Interspecies Communication signal autoinducer-2 (AI-2) to regulate multiple behaviors, the molecular mechanisms of AI-2 recognition and signal transduction remain poorly understood. To date, two types of AI-2 receptors have been identified: LuxP, present in Vibrio spp., and LsrB, first identified in Salmonella enterica serovar Typhimurium. In S. Typhimurium, LsrB is the ligand binding protein of a transport system that enables the internalization of AI-2. Here, using both sequence analysis and structure prediction, we establish a set of criteria for identifying functional AI-2 receptors. We test our predictions experimentally, assaying key species for their abilities to import AI-2 in vivo, and test their LsrB orthologs for AI-2 binding in vitro. Using these experimental approaches, we were able to identify AI-2 receptors in organisms belonging to phylogenetically distinct families such as the Enterobacteriaceae, Rhizobiaceae, and Bacillaceae. Phylogenetic analysis of LsrB orthologs indicates that this pattern could result from one single origin of the functional LsrB gene in a gammaproteobacterium, suggesting possible posterior independent events of lateral gene transfer to the Alphaproteobacteria and Firmicutes. Finally, we used mutagenesis to show that two AI-2-interacting residues are essential for the AI-2 binding ability. These two residues are conserved in the binding sites of all the functional AI-2 binding proteins but not in the non-AI-2-binding orthologs. Together, these results strongly support our ability to identify functional LsrB-type AI-2 receptors, an important step in investigations of this Interspecies signal.
-
luxs quorum sensing more than just a numbers game
Current Opinion in Microbiology, 2003Co-Authors: Karina B. Xavier, Bonnie L BasslerAbstract:Abstract Quorum sensing is a process of bacterial cell-to-cell Communication involving the production and detection of extracellular signaling molecules called autoinducers. Quorum sensing allows populations of bacteria to collectively control gene expression, and thus synchronize group behavior. Processes controlled by quorum sensing are typically ones that are unproductive unless many bacteria act together. Most autoinducers enable intraspecies Communication; however, a recently discovered autoinducer AI-2 has been proposed to serve as a ‘universal signal’ for Interspecies Communication. Studies suggest that AI-2 encodes information in addition to specifics about cell number.
Bonnie L Bassler - One of the best experts on this subject based on the ideXlab platform.
-
saccharomyces cerevisiae requires cff1 to produce 4 hydroxy 5 methylfuran 3 2h one a mimic of the bacterial quorum sensing autoinducer ai 2
Mbio, 2021Co-Authors: Christina M Kraml, Julie S Valastyan, Istvan Pelczer, Thomas Ferrante, Bonnie L BasslerAbstract:ABSTRACT Quorum sensing is a process of cell-to-cell Communication that bacteria use to orchestrate collective behaviors. Quorum sensing depends on the production, release, and detection of extracellular signal molecules called autoinducers (AIs) that accumulate with increasing cell density. While most AIs are species specific, the AI called AI-2 is produced and detected by diverse bacterial species, and it mediates Interspecies Communication. We recently reported that mammalian cells produce an AI-2 mimic that can be detected by bacteria through the AI-2 receptor LuxP, potentially expanding the role of the AI-2 system to interdomain Communication. Here, we describe a second molecule capable of interdomain signaling through LuxP, 4-hydroxy-5-methylfuran-3(2H)-one (MHF), that is produced by the yeast Saccharomyces cerevisiae. Screening the S. cerevisiae deletion collection revealed Cff1p, a protein with no known role, to be required for MHF production. Cff1p is proposed to be an enzyme, with structural similarity to sugar isomerases and epimerases, and substitution at the putative catalytic residue eliminated MHF production in S. cerevisiae. Sequence analysis uncovered Cff1p homologs in many species, primarily bacterial and fungal, but also viral, archaeal, and higher eukaryotic. Cff1p homologs from organisms from all domains can complement a cff1ΔS. cerevisiae mutant and restore MHF production. In all cases tested, the identified catalytic residue is conserved and required for MHF to be produced. These findings increase the scope of possibilities for interdomain interactions via AI-2 and AI-2 mimics, highlighting the breadth of molecules and organisms that could participate in quorum sensing. IMPORTANCE Quorum sensing is a cell-to-cell Communication process that bacteria use to monitor local population density. Quorum sensing relies on extracellular signal molecules called autoinducers (AIs). One AI called AI-2 is broadly made by bacteria and used for Interspecies Communication. Here, we describe a eukaryotic AI-2 mimic, 4-hydroxy-5-methylfuran-3(2H)-one, (MHF), that is made by the yeast Saccharomyces cerevisiae, and we identify the Cff1p protein as essential for MHF production. Hundreds of viral, archaeal, bacterial, and eukaryotic organisms possess Cff1p homologs. This finding, combined with our results showing that homologs from all domains can replace S. cerevisiae Cff1p, suggests that like AI-2, MHF is widely produced. Our results expand the breadth of organisms that may participate in quorum-sensing-mediated interactions.
-
autoinducer 2 a concentration dependent signal for mutualistic bacterial biofilm growth
Molecular Microbiology, 2006Co-Authors: Alexander H Rickard, Bonnie L Bassler, Paul G Egland, Robert J Palmer, David S Blehert, Shawn R Campagna, M F Semmelhack, Paul E KolenbranderAbstract:4,5-Dihydroxy-2,3-pentanedione (DPD), a product of the LuxS enzyme in the catabolism of S-ribosylhomocysteine, spontaneously cyclizes to form autoinducer 2 (AI-2). AI-2 is proposed to be a universal signal molecule mediating Interspecies Communication among bacteria. We show that mutualistic and abundant biofilm growth in flowing saliva of two human oral commensal bacteria, Actinomyces naeslundii T14V and Streptococcus oralis 34, is dependent upon production of AI-2 by S. oralis 34. A luxS mutant of S. oralis 34 was constructed which did not produce AI-2. Unlike wild-type dual-species biofilms, A. naeslundii T14V and an S. oralis 34 luxS mutant did not exhibit mutualism and generated only sparse biofilms which contained a 10-fold lower biomass of each species. Restoration of AI-2 levels by genetic or chemical (synthetic AI-2 in the form of DPD) complementation re-established the mutualistic growth and high biomass characteristic for the wild-type dual-species biofilm. Furthermore, an optimal concentration of DPD was determined, above and below which biofilm formation was suppressed. The optimal concentration was 100-fold lower than the detection limit of the currently accepted AI-2 assay. Thus, AI-2 acts as an Interspecies signal and its concentration is critical for mutualism between two species of oral bacteria grown under conditions that are representative of the human oral cavity.
-
Interspecies Communication in bacteria
Journal of Clinical Investigation, 2003Co-Authors: Michael J Federle, Bonnie L BasslerAbstract:Until recently, bacteria were considered to live rather asocial, reclusive lives. New research shows that, in fact, bacteria have elaborate chemical signaling systems that enable them to communicate within and between species. One signal, termed AI-2, appears to be universal and facilitates Interspecies Communication. Many processes, including virulence factor production, biofilm formation, and motility, are controlled by AI-2. Strategies that interfere with Communication in bacteria are being explored in the biotechnology industry with the aim of developing novel antimicrobials. AI-2 is a particularly attractive candidate for such studies because of its widespread use in the microbial kingdom.
-
luxs quorum sensing more than just a numbers game
Current Opinion in Microbiology, 2003Co-Authors: Karina B. Xavier, Bonnie L BasslerAbstract:Abstract Quorum sensing is a process of bacterial cell-to-cell Communication involving the production and detection of extracellular signaling molecules called autoinducers. Quorum sensing allows populations of bacteria to collectively control gene expression, and thus synchronize group behavior. Processes controlled by quorum sensing are typically ones that are unproductive unless many bacteria act together. Most autoinducers enable intraspecies Communication; however, a recently discovered autoinducer AI-2 has been proposed to serve as a ‘universal signal’ for Interspecies Communication. Studies suggest that AI-2 encodes information in addition to specifics about cell number.
-
the luxs family of bacterial autoinducers biosynthesis of a novel quorum sensing signal molecule
Molecular Microbiology, 2001Co-Authors: Stephan Schauder, Michael G Surette, Kevan M Shokat, Bonnie L BasslerAbstract:Many bacteria control gene expression in response to cell population density, and this phenomenon is called quorum sensing. In Gram-negative bacteria, quorum sensing typically involves the production, release and detection of acylated homoserine lactone signalling molecules called autoinducers. Vibrio harveyi, a Gram-negative bioluminescent marine bacterium, regulates light production in response to two distinct autoinducers (AI-1 and AI-2). AI-1 is a homoserine lactone. The structure of AI-2 is not known. We have suggested previously that V. harveyi uses AI-1 for intraspecies Communication and AI-2 for Interspecies Communication. Consistent with this idea, we have shown that many species of Gram-negative and Gram-positive bacteria produce AI-2 and, in every case, production of AI-2 is dependent on the function encoded by the luxS gene. We show here that LuxS is the AI-2 synthase and that AI-2 is produced from S-adenosylmethionine in three enzymatic steps. The substrate for LuxS is S-ribosylhomocysteine, which is cleaved to form two products, one of which is homocysteine, and the other is AI-2. In this report, we also provide evidence that the biosynthetic pathway and biochemical intermediates in AI-2 biosynthesis are identical in Escherichia coli, Salmonella typhimurium, V. harveyi, Vibrio cholerae and Enterococcus faecalis. This result suggests that, unlike quorum sensing via the family of related homoserine lactone autoinducers, AI-2 is a unique, 'universal' signal that could be used by a variety of bacteria for Communication among and between species.
Stephen T. Miller - One of the best experts on this subject based on the ideXlab platform.
-
processing the Interspecies quorum sensing signal autoinducer 2 ai 2 characterization of phospho s 4 5 dihydroxy 2 3 pentanedione isomerization by lsrg protein
Journal of Biological Chemistry, 2011Co-Authors: Joao C Marques, Stephen T. Miller, M F Semmelhack, Pedro Lamosa, Caitlin Russell, Rita Ventura, Christopher D Maycock, Karina B. XavierAbstract:The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is the precursor of the signal molecule autoinducer-2 (AI-2). AI-2 mediates Interspecies Communication and facilitates regulation of bacterial behaviors such as biofilm formation and virulence. A variety of bacterial species have the ability to sequester and process the AI-2 present in their environment, thereby interfering with the cell-cell Communication of other bacteria. This process involves the AI-2-regulated lsr operon, comprised of the Lsr transport system that facilitates uptake of the signal, a kinase that phosphorylates the signal to phospho-DPD (P-DPD), and enzymes (like LsrG) that are responsible for processing the phosphorylated signal. Because P-DPD is the intracellular inducer of the lsr operon, enzymes involved in P-DPD processing impact the levels of Lsr expression. Here we show that LsrG catalyzes isomerization of P-DPD into 3,4,4-trihydroxy-2-pentanone-5-phosphate. We present the crystal structure of LsrG, identify potential catalytic residues, and determine which of these residues affects P-DPD processing in vivo and in vitro. We also show that an lsrG deletion mutant accumulates at least 10 times more P-DPD than wild type cells. Consistent with this result, we find that the lsrG mutant has increased expression of the lsr operon and an altered profile of AI-2 accumulation and removal. Understanding of the biochemical mechanisms employed by bacteria to quench signaling of other species can be of great utility in the development of therapies to control bacterial behavior.
-
Identification of functional LsrB-like autoinducer-2 receptors.
Journal of Bacteriology, 2009Co-Authors: C Pereira, Patricia H Brito, Anna K. De Regt, Stephen T. Miller, Karina B. XavierAbstract:Although a variety of bacterial species have been reported to use the Interspecies Communication signal autoinducer-2 (AI-2) to regulate multiple behaviors, the molecular mechanisms of AI-2 recognition and signal transduction remain poorly understood. To date, two types of AI-2 receptors have been identified: LuxP, present in Vibrio spp., and LsrB, first identified in Salmonella enterica serovar Typhimurium. In S. Typhimurium, LsrB is the ligand binding protein of a transport system that enables the internalization of AI-2. Here, using both sequence analysis and structure prediction, we establish a set of criteria for identifying functional AI-2 receptors. We test our predictions experimentally, assaying key species for their abilities to import AI-2 in vivo, and test their LsrB orthologs for AI-2 binding in vitro. Using these experimental approaches, we were able to identify AI-2 receptors in organisms belonging to phylogenetically distinct families such as the Enterobacteriaceae, Rhizobiaceae, and Bacillaceae. Phylogenetic analysis of LsrB orthologs indicates that this pattern could result from one single origin of the functional LsrB gene in a gammaproteobacterium, suggesting possible posterior independent events of lateral gene transfer to the Alphaproteobacteria and Firmicutes. Finally, we used mutagenesis to show that two AI-2-interacting residues are essential for the AI-2 binding ability. These two residues are conserved in the binding sites of all the functional AI-2 binding proteins but not in the non-AI-2-binding orthologs. Together, these results strongly support our ability to identify functional LsrB-type AI-2 receptors, an important step in investigations of this Interspecies signal.
M F Semmelhack - One of the best experts on this subject based on the ideXlab platform.
-
processing the Interspecies quorum sensing signal autoinducer 2 ai 2 characterization of phospho s 4 5 dihydroxy 2 3 pentanedione isomerization by lsrg protein
Journal of Biological Chemistry, 2011Co-Authors: Joao C Marques, Stephen T. Miller, M F Semmelhack, Pedro Lamosa, Caitlin Russell, Rita Ventura, Christopher D Maycock, Karina B. XavierAbstract:The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is the precursor of the signal molecule autoinducer-2 (AI-2). AI-2 mediates Interspecies Communication and facilitates regulation of bacterial behaviors such as biofilm formation and virulence. A variety of bacterial species have the ability to sequester and process the AI-2 present in their environment, thereby interfering with the cell-cell Communication of other bacteria. This process involves the AI-2-regulated lsr operon, comprised of the Lsr transport system that facilitates uptake of the signal, a kinase that phosphorylates the signal to phospho-DPD (P-DPD), and enzymes (like LsrG) that are responsible for processing the phosphorylated signal. Because P-DPD is the intracellular inducer of the lsr operon, enzymes involved in P-DPD processing impact the levels of Lsr expression. Here we show that LsrG catalyzes isomerization of P-DPD into 3,4,4-trihydroxy-2-pentanone-5-phosphate. We present the crystal structure of LsrG, identify potential catalytic residues, and determine which of these residues affects P-DPD processing in vivo and in vitro. We also show that an lsrG deletion mutant accumulates at least 10 times more P-DPD than wild type cells. Consistent with this result, we find that the lsrG mutant has increased expression of the lsr operon and an altered profile of AI-2 accumulation and removal. Understanding of the biochemical mechanisms employed by bacteria to quench signaling of other species can be of great utility in the development of therapies to control bacterial behavior.
-
autoinducer 2 a concentration dependent signal for mutualistic bacterial biofilm growth
Molecular Microbiology, 2006Co-Authors: Alexander H Rickard, Bonnie L Bassler, Paul G Egland, Robert J Palmer, David S Blehert, Shawn R Campagna, M F Semmelhack, Paul E KolenbranderAbstract:4,5-Dihydroxy-2,3-pentanedione (DPD), a product of the LuxS enzyme in the catabolism of S-ribosylhomocysteine, spontaneously cyclizes to form autoinducer 2 (AI-2). AI-2 is proposed to be a universal signal molecule mediating Interspecies Communication among bacteria. We show that mutualistic and abundant biofilm growth in flowing saliva of two human oral commensal bacteria, Actinomyces naeslundii T14V and Streptococcus oralis 34, is dependent upon production of AI-2 by S. oralis 34. A luxS mutant of S. oralis 34 was constructed which did not produce AI-2. Unlike wild-type dual-species biofilms, A. naeslundii T14V and an S. oralis 34 luxS mutant did not exhibit mutualism and generated only sparse biofilms which contained a 10-fold lower biomass of each species. Restoration of AI-2 levels by genetic or chemical (synthetic AI-2 in the form of DPD) complementation re-established the mutualistic growth and high biomass characteristic for the wild-type dual-species biofilm. Furthermore, an optimal concentration of DPD was determined, above and below which biofilm formation was suppressed. The optimal concentration was 100-fold lower than the detection limit of the currently accepted AI-2 assay. Thus, AI-2 acts as an Interspecies signal and its concentration is critical for mutualism between two species of oral bacteria grown under conditions that are representative of the human oral cavity.
Baolin Sun - One of the best experts on this subject based on the ideXlab platform.
-
luxs ai 2 system is involved in antibiotic susceptibility and autolysis in staphylococcus aureus nctc 8325
International Journal of Antimicrobial Agents, 2013Co-Authors: Ting Xue, Liping Zhao, Baolin SunAbstract:Current treatment for Staphylococcus aureus infections relies heavily upon the cell wall synthesis inhibitor antibiotics such as penicillin, oxacillin, vancomycin and teicoplanin. Increasing antibiotic resistance requires the development of new approaches to combating infection. Autoinducer-2 (AI-2) exists widely both in Gram-negative and Gram-positive pathogens and is suggested as a universal language for intraspecies and Interspecies Communication. This study demonstrates the association between AI-2 signalling and cell wall synthesis inhibitor antibiotic susceptibility in S. aureus. In addition, a luxS mutant exhibited decreased autolysis and upregulated vancomycin resistance-associated VraRS two-component regulatory system. This finding may provide novel clues for antimicrobial therapy in S. aureus infection.
-
staphylococcus aureus autoinducer 2 quorum sensing decreases biofilm formation in an icar dependent manner
BMC Microbiology, 2012Co-Authors: Liping Zhao, Ting Xue, Baolin SunAbstract:Staphylococcus aureus is an important pathogen that causes biofilm-associated infection in humans. Autoinducer 2 (AI-2), a quorum-sensing (QS) signal for Interspecies Communication, has a wide range of regulatory functions in both Gram-positive and Gram-negative bacteria, but its exact role in biofilm formation in S. aureus remains unclear. Here we demonstrate that mutation of the AI-2 synthase gene luxS in S. aureus RN6390B results in increased biofilm formation compared with the wild-type (WT) strain under static, flowing and anaerobic conditions and in a mouse model. Addition of the chemically synthesized AI-2 precursor in the luxS mutation strain (ΔluxS) restored the WT phenotype. Real-time RT-PCR analysis showed that AI-2 activated the transcription of icaR, a repressor of the ica operon, and subsequently a decreased level of icaA transcription, which was presumably the main reason why luxS mutation influences biofilm formation. Furthermore, we compared the roles of the agr-mediated QS system and the LuxS/AI-2 QS system in the regulation of biofilm formation using the ΔluxS strain, RN6911 and the Δagr ΔluxS strain. Our data indicate a cumulative effect of the two QS systems on the regulation of biofilm formation in S. aureus. These findings demonstrate that AI-2 can decrease biofilm formation in S. aureus via an icaR-activation pathway. This study may provide clues for therapy in S. aureus biofilm-associated infection.
