Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.184 (LasR)
 897 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Quorum sensing (QS) governs the production of virulence factors and the architecture and sodium dodecyl sulphate (SDS) resistance of biofilm-grown Pseudomonas aeruginosa. P. aeruginosa QS requires two transcriptional activator proteins known as LasR and RhlR and their cognate autoinducers PAI-1 (N-(3-oxododecanoyl)-L-homoserine lactone) and PAI-2 (N-butyryl-L-homoserine lactone) respectively. This study provides evidence of QS control of genes essential for relieving oxidative stress. Mutants devoid of one or both autoinducers were more sensitive to hydrogen peroxide and phenazine methosulphate, and some PAI mutant strains also demonstrated decreased expression of two superoxide dismutases (SODs), Mn-SOD and Fe-SOD, and the major catalase, KatA. The expression of sodA (encoding Mn-SOD) was particularly dependent on PAI-1, whereas the influence of autoinducers on Fe-SOD and KatA levels was also apparent but not to the degree observed with Mn-SOD. beta-Galactosidase reporter fusion results were in agreement with these findings. Also, the addition of both PAIs to suspensions of the PAI-1/2-deficient double mutant partially restored KatA activity, while the addition of PAI-1 only was sufficient for full restoration of Mn-SOD activity. In biofilm studies, catalase activity in wild-type bacteria was significantly reduced relative to planktonic bacteria; catalase activity in the PAI mutants was reduced even further and consistent with relative differences observed between each strain grown planktonically. While wild-type and mutant biofilms contained less catalase activity, they were more resistant to hydrogen peroxide treatment than their respective planktonic counterparts. Also, while catalase was implicated as an important factor in biofilm resistance to hydrogen peroxide insult, other unknown factors seemed potentially important, as PAI mutant biofilm sensitivity appeared not to be incrementally correlated to catalase levels.
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PMID:Quorum sensing in Pseudomonas aeruginosa controls expression of catalase and superoxide dismutase genes and mediates biofilm susceptibility to hydrogen peroxide. 1059 32

Luminescence in Vibrio fischeri is controlled by a population density-responsive regulatory mechanism called quorum sensing. Elements of the mechanism include: LuxI, an acyl-homoserine lactone (acyl-HSL) synthase that directs synthesis of the diffusible signal molecule, 3-oxo-hexanoyl-HSL (V. fischeri autoinducer-1, VAI-1); LuxR, a transcriptional activator protein necessary for response to VAI-1; GroEL, which is necessary for production of active LuxR; and AinS, an acyl-HSL synthase that catalyzes the synthesis of octanoyl-HSL (VAI-2). The population density-dependent accumulation of VAI-1 triggers induction of lux operon (luxICDABEG; genes for luminescence enzymes and for LuxI) transcription and luminescence by binding to LuxR, forming a complex that facilitates the association of RNA polymerase with the luxoperon promoter. VAI-2, which apparently interferes with VAI-1 binding to LuxR, operates to limit premature luxoperon induction. Hierarchical control is imposed on the system by 3':5'-cyclic AMP (cAMP) and cAMP receptor protein (CRP), which are necessary for activated expression of luxR. Several non-lux genes in V. fischeri are controlled by LuxR and VAI-1. Quorum regulation in V. fischeri serves as a model for LuxI/LuxR-type quorum sensing systems in other gram-negative bacteria.
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PMID:Quorum regulation of luminescence in Vibrio fischeri. 1094 79

Burkholderia multivorans ATCC 17616 ordinarily produces insufficient amounts of N-acyl homoserine lactones (AHLs) to promote AHL-dependent formation of the pigment violacein by the reporter strain Chromobacterium violaceum CV026. We have isolated AHL-overproducing mutants of strain 17616 by screening for variants which do cross-feed AHLs to strain CV026. Nucleotide-sequence analysis of the bmuIR locus which specifies AHL synthase (BmuI) and AHL-binding transcriptional activator protein (BmuR) indicated that the increased capacity to produce AHLs was not a consequence of changes upstream or internal to the bmuI or bmuR genes. We conclude that the mutations leading to AHL overproduction lie outside the bmuI/bmuR locus.
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PMID:Characterization of N-acyl homoserine lactone overproducing mutants of Burkholderia multivorans ATCC 17616. 1181 64

The Pseudomonas aeruginosa LasR protein functions in concert with N-3-oxo-dodecanoyl-L-homoserine lactone (3O-C(12)-HSL) to coordinate the expression of target genes, including many genes that encode virulence factors, with cell density. We used a LexA-based protein interaction assay to demonstrate that LasR forms multimers only when 3O-C(12)-HSL is present. A series of LasR molecules containing internal deletions or substitutions in single, conserved amino acid residues indicated that the N-terminal portion of LasR is required for multimerization. Studies performed with these mutant versions of LasR demonstrated that the ability of LasR to multimerize correlates with its ability to function as a transcriptional activator of lasI, a gene known to be tightly regulated by the LasR-3O-C(12)-HSL regulatory system. A LasR molecule that carries a C-terminal deletion can function as a dominant-negative mutant in P. aeruginosa, as shown by its ability to decrease expression of lasB, another LasR-3O-C(12)-HSL target gene. Taken together, our data strongly support the hypothesis that LasR functions as a multimer in vivo.
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PMID:LasR, a transcriptional activator of Pseudomonas aeruginosa virulence genes, functions as a multimer. 1216 17

Burkholderia ambifaria BC-F, a biocontrol strain reported previously to exhibit broad-spectrum antifungal activity, was highly active in formation of N-acyl homoserine lactones (AHLs). We constructed AHL-deficient derivatives of strain BC-F in which the genes specifying AHL synthase (bafI) and AHL-binding transcriptional activator (bafR) were inactivated by allelic exchange. The resulting AHL-deficient mutants had decreased antifungal activity.
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PMID:AHL-deficient mutants of Burkholderia ambifaria BC-F have decreased antifungal activity. 1457 Feb 65

Pseudomonas syringae forms large cell aggregates that are more stress tolerant than solitary cells during epiphytic growth on plants. The differential survival of aggregates on leaves suggests that epiphytic fitness traits may be controlled in a density-dependent manner via cell-cell signaling. We investigated this hypothesis in P. syringae B728a. Synthesis of N-acyl-homoserine lactone (AHL), 3-oxo-hexanoyl homoserine lactone, and the expression of the gene encoding AHL synthase ahlI were maximal at high cell concentrations. The expression of the AHL regulator ahlR, in contrast, was similar at all cell concentrations. A screen of Tn5 mutants revealed that P. syringae B728a requires a novel transcriptional activator for AHL production. This regulator, which belongs to the TetR family, was also required for epiphytic fitness and has been designated AefR (for AHL and epiphytic fitness regulator). The expression of ahlI was greatly reduced in both aefR- and gacA- mutants and was completely restored in either mutant after addition of exogenous AHL. In contrast, the expression of aefR was not reduced in either gacS- or gacA- mutants. Thus, AefR appears to positively regulate AHL production independently of the regulators GacS/GacA and also controls traits in P. syringae B728a that are required for epiphytic colonization.
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PMID:Regulation of AHL production and its contribution to epiphytic fitness in Pseudomonas syringae. 1514 56

Burkholderia glumae BGR1 produces a broad-host range phytotoxin, called toxoflavin, which is a key pathogenicity factor in rice grain rot and wilt in many field crops. Our molecular and genetic analyses of toxoflavin-deficient mutants demonstrated that gene clusters for toxoflavin production consist of four transcriptional units. The toxoflavin biosynthesis genes were composed of five genes, toxA to toxE, as Suzuki et al. (2004) reported previously. Genes toxF to toxI, which are responsible for toxoflavin transport, were polycistronic and similar to the genes for resistance-nodulation-division (RND) efflux systems. Using Tn3-gusA reporter fusions, we found that ToxR, a LysR-type regulator, regulates both the toxABCDE and toxFGHI operons in the presence of toxoflavin as a coinducer. In addition, the expression of both operons required a transcriptional activator, ToxJ, whose expression is regulated by quorum sensing. TofI, a LuxI homologue, was responsible for the biosynthesis of both N-hexanoyl homoserine lactone and N-octanoyl homoserine lactone (C8-HSL). C8-HSL and its cognate receptor TofR, a LuxR homologue, activated toxJ expression. This is the first report that quorum sensing is involved in pathogenicity by the regulation of phytotoxin biosynthesis and its transport in plant pathogenic bacteria.
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PMID:Quorum sensing and the LysR-type transcriptional activator ToxR regulate toxoflavin biosynthesis and transport in Burkholderia glumae. 1552 77

The production of several virulence factors by Pseudomonas aeruginosa is regulated through the hierarchical cell-density dependent quorum sensing (QS) systems las and rhl. A third component of the QS hierarchy, the Pseudomonas quinolone signal PQS, also controls the expression of several genes. We previously described P. aeruginosa PtxR as a transcriptional activator of the exotoxin A gene toxA. Here, we provide evidence that PtxR regulates the production of other virulence factors. Mutation of ptxR in PAO1 increased pyocyanin production. This increase was reduced in the presence of a ptxR plasmid. Throughout the growth cycle, PtxR reduced the expression of the pyocyanin operon phzA1-G1 but not phzA2-G2. As pyocyanin production is stringently controlled by QS, we examined the effect of PtxR on QS-related genes in PAO1. PtxR also reduced the expression of the PQS synthesis operon pqsABCDE. ptxR mutation increased the expression of the rhamnolipid synthesis gene rhlA but decreased lasB expression. The expression of the RhlI synthase gene rhlI and the production of the C(4)-HSL autoinducer were increased in the ptxR mutant, while the expression of the LasI synthase gene lasI and the production of 3OC(12)-HSL were reduced. These results suggest that PtxR negatively regulates the expression of the rhamnolipid and pyocyanin genes through rhlI and the pqsABCDE operon while it positively regulates the expression of lasB through lasI.
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PMID:PtxR modulates the expression of QS-controlled virulence factors in the Pseudomonas aeruginosa strain PAO1. 1680 94

The biological control bacterium Pseudomonas chlororaphis (aureofaciens) strain 30-84 employs two quorum sensing (QS) systems: PhzR/PhzI regulates the production of the antibiotics phenazine-1-carboxylic acid, 2-hydroxy-phenazine-1-carboxylic acid, and 2-hydroxy-phenazine, whereas CsaR/CsaI regulates currently unknown aspects of the cell surface. Previously characterized derivatives of strain 30-84 with mutations in each QS system and in the phenazine biosynthetic genes were screened for their ability to form surface-attached biofilm populations in vitro, using microtiter plate and flow cell biofilm assays, and on seeds and roots. Results from in vitro, seed, and root studies demonstrated that the PhzR/PhzI and the CsaR/CsaI QS regulatory systems contribute to the establishment of biofilms, with mutations in PhzR/PhzI having a significantly greater effect than mutations in CsaR/CsaI. Interestingly, phenazine antibiotic production was necessary for biofilm formation to the same extent as the PhzR/PhzI QS system, suggesting the loss of phenazines was responsible for the majority of the biofilm defect in these mutants. In vitro analysis indicated that genetic complementation or AHL addition to the growth medium restored the ability of the AHL synthase phzI mutant to form biofilms. However, only phenazine addition or genetic complementation of the phenazine biosynthetic mutation in trans restored biofilm formation by mutants defective in the transcriptional activator phzR or the phzB structural mutant. QS and phenazine production were also involved in the establishment of surface-attached populations on wheat seeds and plant roots, and, as observed in vitro, the addition of AHL extracts restored the ability of phzI mutants, but not phzR mutants, to form surface attached populations on seeds. Similarly, the presence of the wild type in mixtures with the mutants restored the ability of the mutants to colonize wheat roots, demonstrating that AHL and/or phenazine production by the wild-type population could complement the AHL- and phenazine-deficient mutants in situ. Together, these data demonstrate that both QS systems are involved in the formation of surface-attached populations required for biofilm formation by P. chlororaphis strain 30-84, and indicate a new role for phenazine antibiotics in rhizosphere community development beyond inhibition of other plant-associated microorganisms.
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PMID:Quorum sensing and phenazines are involved in biofilm formation by Pseudomonas chlororaphis (aureofaciens) strain 30-84. 1689 5

Chemical coordination of gene expression among bacteria as a function of population density is regulated by a mechanism known as 'quorum sensing' (QS). QS in Pseudomonas aeruginosa, an opportunistic pathogen that causes disease in immunocompromised patients, is mediated by binding of the transcriptional activator, LasR, to its ligand, 3-oxo-C(12)-HSL, leading to population-wide secretion of virulence factors and biofilm formation. We have targeted QS in P. aeruginosa with a set of electrophilic probes designed to covalently bind Cys79 in the LasR binding pocket, leading to specific inhibition of QS-regulated gene expression and concomitant reduction of virulence factor secretion and biofilm formation. This first example of covalent modification of a QS receptor provides a new tool to study molecular mechanisms of bacterial group behavior and could lead to new strategies for targeting bacterial virulence.
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PMID:Covalent inhibition of bacterial quorum sensing. 1958 89


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