Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A total of 121 uropathogenic Pseudomonas aeruginosa strains were examined for production of several virulence-related factors. These strains were distributed in five predominant O-serotypes, i.e. O 4, O 12, O 11, O 6 and O 5, which accounted respectively for 23.9, 23.1, 12.3, 8.2 and 5.7% of isolates. Pyochelin and pyoverdin siderophores were produced by most of the isolates, defective variants occurring at very low frequency (2.4% for pyochelin and 7.4% for pyoverdin). Adherence to uroepithelial cells and production of cytotoxins was demonstrated in 52.8 and 67.7% of the strains, respectively, with higher frequencies for epidemiologically related strains belonging to serotypes O 4 and O 12. Titration of total proteases, elastase and phospholipase C revealed a high degree of heterogeneity among isolates. However, examination of individual O-serotypes by exoenzyme production showed that elevated levels of total proteases and elastase were characteristics of serotypes of minor numerical importance, i.e. O 1, O 10, O 11 and O 17, whilst low levels of elastase were produced by strains belonging to the predominant serotypes, namely O 4 and O 12. Moreover, epidemiologically related strains belonging to serotypes O 4 and O 12 appeared more homogeneous than the whole serogroup, when compared with other groups on the basis of exoenzyme levels.
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PMID:Virulence determinants in Pseudomonas aeruginosa strains from urinary tract infections. 158 73

Phospholipase C has been increasingly recognized as a significant virulence determinant in the pathogenesis of Gram-negative and Gram-positive infections. Pseudomonas aeruginosa carries two, non-tandem genes encoding phospholipase C (PLC) activity. One PLC (PLC-H) haemolyses human and sheep erythrocytes while the other is not haemolytic for these kinds of red blood cells. It was previously determined that the synthesis of both PLCs is regulated by inorganic phosphate (Pi), but little else was known regarding the regulation of these potentially important virulence determinants of P. aeruginosa. In this report, data are presented demonstrating that both PLC genes are regulated at the transcriptional level by Pi and by a P. aeruginosa homologue of the positive regulator of genes in the Pi regulon of Escherichia coli, i.e. PhoB. In addition to Pi, it is also shown in this report that the synthesis of both PLC-H and PLC-N is induced by compounds which are not only derived from the substrate product of both enzymes, i.e. phosphorylcholine, but are also known osmoprotectants in eukaryotic and prokaryotic cells. The osmoprotective derivatives of phosphorylcholine which induce the synthesis of PLC in P. aeruginosa include choline, glycine betaine, and dimethylglycine, but not sarcosine (monomethylglycine) or glycine. By constructing mutants which are deficient in the production of each separate PLC and in the production of PhoB it was determined that induction of PLC-H by the osmoprotective compounds is independent of Pi concentration and PhoB, while induction of PLC-N by these compounds requires Pi-deficient conditions and PhoB.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Osmoprotectants and phosphate regulate expression of phospholipase C in Pseudomonas aeruginosa. 160 66

The adherence of Pseudomonas aeruginosa PAO1 to primary cultures of cystic fibrosis nasal polyp (CFNP), normal human nasal polyp (NHNP), and immortalized CF and normal cell lines was studied. PAO1 bound significantly more to primary CFNP cells than to NHNP cells as the mean adherence +/- standard deviation of 5 x 10(7) CFU of 35S-labeled bacteria per ml per well was 15.09 x 10(6) +/- 4.25 x 10(6) CFU/ml per well and 7.62 x 10(6) +/- 2.11 x 10(6) CFU/ml per well, respectively (Mann-Whitney U test, P less than 0.0001). There was no significant difference in PAO1 adherence to the immortalized CF and normal cell lines. The primary CFNP cells had more receptors (115 per cell) than did NHNP cells (34 per cell). P. aeruginosa binding to CFNP was blocked by GlcNAc, NeuAc, L-Fuc, and D-Gal, while binding to NHNP was blocked only by GlcNAc, suggesting that receptors on the two cell types were qualitatively different. Pseudomonas supernatants containing protease, phospholipase C, and neuraminidase activity increased adherence to CFNP and NHNP cells. The Pseudomonas exoproducts modified epithelial cell glycoconjugates, as characterized by binding of fluorescein isothiocyanate-labeled lectins and the release of sialic acid. There was minimal release of fibronectin by the bacterial supernatants. The affinity of P. aeruginosa for CF epithelial cells appeared to be due to an increased number of receptors and modification of the epithelial cell surface by P. aeruginosa exoproducts that exposed asialoganglioside binding sites.
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PMID:Comparison of adherence of Pseudomonas aeruginosa to respiratory epithelial cells from cystic fibrosis patients and healthy subjects. 161 46

Choline, acetylcholine and betaine used as the sole carbon, nitrogen or carbon and nitrogen source increase cholinesterase activity in addition to phosphorylcholine phosphatase and phospholipase C activities in Pseudomonas aeruginosa. The cholinesterase activity catalyses the hydrolysis of acetylthiocholine (Km approx. 0.13 mM) and propionylthiocholine (Km approx. 0.26 mM), but not butyrylthiocholine, which is a pure competitive inhibitor (Ki 0.05 mM). Increasing choline concentrations in the assay mixture decreased the affinity of cholinesterase for acetylthiocholine, but in all cases prevented inhibition raised by high substrate concentrations. Considering the properties of these enzymes, and the fact that in the corneal epithelium there exists a high acetylcholine concentration and that Pseudomonas aeruginosa produces corneal infection, it is proposed that these enzymes acting coordinately might contribute to the breakdown of the corneal epithelial membrane.
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PMID:Pseudomonas aeruginosa cholinesterase and phosphorylcholine phosphatase: two enzymes contributing to corneal infection. 165 99

In Pseudomonas aeruginosa, the genes pilB, pilC, and pilD encode proteins necessary for posttranslational modification and assembly of pilin monomers into pilus organelles (D. Nunn, S. Bergman, and S. Lory, J. Bacteriol. 172:2911-2919, 1990). We show that PilD, encoding a putative pilin-specific leader peptidase, also controls export of alkaline phosphatase, phospholipase C, elastase, and exotoxin A. pilD mutants accumulate these proteins in the periplasmic space, while secretion of periplasmic and outer membrane proteins appears to be normal. The periplasmic form of exotoxin A was fully mature in size, contained all cysteines in disulfide bonds, and was toxic in a tissue culture cytotoxicity assay, suggesting that in pilD mutants, exotoxin A was folded into its native conformation. The function of the other two accessory proteins, PilB and PilC, appears to be restricted to pilus biogenesis, and strains carrying mutations in their respective genes do not show an export defect. These studies show that in addition to cleaving the leader sequence from prepilin, PilD has an additional role in secretion of proteins that are released from P. aeruginosa into the surrounding media. PilD most likely functions as a protease that is involved in processing and assembly of one or more components of the membrane machinery necessary for the later stages of protein extracellular localization.
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PMID:Multiple roles of the pilus biogenesis protein pilD: involvement of pilD in excretion of enzymes from Pseudomonas aeruginosa. 167 84

K1 is a monoclonal antibody that reacts with a cell surface antigen (CAK1) found in human mesothelia and nonmucinous ovarian tumors. In this article, the characteristics of the CAK1 antigen have been examined in detail. Using immunofluorescence microscopy, we have found that the CAK1 signal is removed from the cell surface by treatment with proteases or by phosphatidylinositol-phospholipase C, but not by neuraminidase and beta-galactosidase. The phosphatidylinositol-phospholipase C-released material was found to contain the CAK1 antigen which was detected by a competition radioimmunoassay. The phosphatidylinositol-phospholipase C-released CAK1 antigen was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting and found to be approximately 40 kDa protein. The CAK1-K1 antibody complex remains on the cell surface and is poorly internalized, as shown by an acid wash immunofluorescence internalization assay. An immunotoxin composed of K1 and Lys-PE40, a mutant form of Pseudomonas exotoxin lacking the cell binding domain, was not cytotoxic, supporting the conclusion that the CAK1-K1 antibody complex is not internalized. However, an immunotoxin composed of K1 and native Pseudomonas exotoxin was selectively cytotoxic to cells expressing the CAK1 antigen. This cytotoxicity is due to the fact that domain I of Pseudomonas exotoxin promotes internalization of antigens which are not internalized or bound to antibody alone. Our results suggest that CAK1 is a polypeptide that is expressed on mesothelial cells and many ovarian cancers, and that K1 may be useful as a targeting agent for the immunotherapy of human ovarian cancer.
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PMID:Characterization of the antigen (CAK1) recognized by monoclonal antibody K1 present on ovarian cancers and normal mesothelium. 172 78

We have isolated and characterized four toxin A excretion-deficient mutants of Pseudomonas aeruginosa PAO1. Similar to previously described mutants (B. Wretlind and O. R. Pavlovskis, J. Bacteriol. 158:801-808, 1984), the mutants appear to have a pleiotropic defect in the excretion of several extracellular products, including toxin A, elastase, alkaline phosphatase, and phospholipase C. However, the mutants are not defective in the excretion of either alkaline protease or exoenzyme S. We also examined the localization and processing of toxin A in these mutants by using pulse-labeling experiments. Mature toxin A was found to be localized to the membranes only. Our results suggest that toxin A is localized to the outer membrane but is not exposed to the extracellular surfaces of the outer membranes. The results also suggest that toxin A obtained from the excretion-deficient mutants has intact disulfide bonds.
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PMID:Isolation and characterization of toxin A excretion-deficient mutants of Pseudomonas aeruginosa PAO1. 173 Apr 83

A chronic pulmonary infection model was used to induce conversion to the mucoid phenotype by Pseudomonas aeruginosa PAO. At 6 months after initial inoculation, organisms isolated from infected lungs demonstrated the mucoid phenotype. Significant decreases (P less than .01) were seen in the levels of exotoxin A, exoenzyme S, phospholipase C, and pyochelin produced by the mucoid P. aeruginosa PAO rat lung isolates that returned to parental levels after reversion to the nonmucoid phenotype. In addition, lipopolysaccharide of the mucoid PAO lung isolates failed to react with serotype B-specific antibody in contrast to the original PAO and the revertant PAO organisms. Digestion of chromosomal DNA and hybridization with P. aeruginosa virulence factor-specific probes demonstrated that conversion to the mucoid phenotype was associated with rearrangement of chromosomal DNA upstream of the exotoxin A gene. Analysis of DNA from revertant organisms revealed hybridization patterns identical to the original PAO organism.
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PMID:In vivo regulation of virulence in Pseudomonas aeruginosa associated with genetic rearrangement. 182 96

Growth and conversion to the mucoid phenotype by nonmucoid Pseudomonas aeruginosa PAO1 was studied in a chemostat system under conditions designed to reflect those likely to be present during chronic infection in the lung in cystic fibrosis patients. Mucoid variants were consistently isolated during continuous culture in the presence of 0.3 M NaCl or 5 or 10% glycerol. Mucoid subpopulations were also detected under conditions of carbon, nitrogen, or phosphate limitation. During carbon or nitrogen limitation, mucoid conversion was dependent upon the choice of substrate. Phosphate-limited cultures exhibited an inverse relationship between culture growth rate and number of mucoid organisms detected. Mucoid variants were not detected when dilution rates (D) exceeded 0.173 h-1. Conversely, at a D of 0.044 h-1, 40% of the population expressed the mucoid phenotype. Phosphorylcholine, a product of phospholipase C activity on the major lung surfactant phosphatidylcholine, was also used as a growth substrate in nutrient limitation studies. Under all conditions, growth of PAO1 supplied with phosphorylcholine resulted in isolation of mucoid variants, indicating that the lung may provide at least one nutrient source conducive to mucoid conversion. Continuous culture also resulted in detection of a phage associated with strain PAO1. High titers of phage were present under all conditions, including those which yielded no mucoid organisms, suggesting that environmental conditions rather than the phage regulated the appearance of mucoid variants.
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PMID:Environmental conditions which influence mucoid conversion Pseudomonas aeruginosa PAO1. 189 4

Previous studies in our laboratory have indicated that naturally resistant, inbred DBA/2J mice mount a greater serum antibody response to Pseudomonas aeruginosa 19660 than susceptible C57BL/6J mice. However, the specificity of the antibody produced was not known. The present study examines the specificity and kinetics of the humoral response of these mouse strains to potential virulence factors produced by the organism during both a primary and a secondary corneal infection administered 4 weeks after the primary infection. Serum antibody levels specific for lipopolysaccharide (LPS), exotoxin A, phospholipase C (PLC), alkaline protease, elastase, and flagella were measured by enzyme-linked immunosorbent assay. Little or no antibody to either alkaline protease or elastase was detected during either primary or secondary infection. Immunoglobulin G (IgG) antibodies specific to exotoxin A, PLC, and flagella were detected 2 weeks after primary infection, and a rapid response to these antigens was measured 1 week after secondary infection. During primary infection, detectable LPS-specific antibody was only IgM, while IgG appeared only after secondary infection. The kinetics of the humoral response in susceptible C57BL/6J mice were similar to those in resistant DBA/2J mice, although the magnitude of the response varied according to the antigen tested. These results indicate that LPS, exotoxin A, PLC, and flagella are present or produced in amounts that are immunogenic during corneal infection by P. aeruginosa 19660 in the mouse strains tested.
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PMID:Serum antibody response to Pseudomonas aeruginosa antigens during corneal infection. 190 70


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