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

Whereas bacteria in the genus Legionella have emerged as relatively frequent causes of pneumonia, the mechanisms underlying their pathogenicity are obscure. The legionellae are facultative intracellular pathogens which multiply within the phagosome of mononuclear phagocytes and are not killed efficiently by polymorphonuclear leukocytes. The functional defects that might permit the intracellular survival of the legionellae have remained an enigma until recently. Phagosome-lysosome fusion is inhibited by a single strain (Philadelphia 1) of Legionella pneumophila serogroup 1, but not by other strains of L. pneumophila or other species. It has been found that following the ingestion of Legionella organisms, the subsequent activation of neutrophils and monocytes in response to both soluble and particulate stimuli is profoundly impaired and the bactericidal activity of these cells is attenuated, suggesting that Legionella bacterial cell-associated factors have an inhibitory effect on phagocyte activation. Two factors elaborated by the legionellae which inhibit phagocyte activation have been described. First, the Legionella (cyto)toxin blocks neutrophil oxidative metabolism in response to various agonists by an unknown mechanism. Second, L. micdadei bacterial cells contain a phosphatase which blocks superoxide anion production by stimulated neutrophils. The Legionella phosphatase disrupts the formation of critical intracellular second messengers in neutrophils. In addition to the toxin and phosphatase, several other moieties that may serve as virulence factors by promoting cell invasion or intracellular survival and multiplication are elaborated by the legionellae. Molecular biological studies show that a cell surface protein named Mip is necessary for the efficient invasion of monocytes. A possible role for a Legionella phospholipase C as a virulence factor is still largely theoretical. L. micdadei contains an unusual protein kinase which catalyzes the phosphorylation of eukaryotic substrates, including phosphatidylinositol and tubulin. Since the phosphorylation of either phosphatidylinositol or tubulin might compromise phagocyte activation and bactericidal functions, this enzyme may well be a virulence factor. Administration of the L. pneumophila exoprotease induces lesions resembling those of Legionella pneumonia and kills guinea pigs, suggesting that this protein plays a role in the pathogenesis of legionellosis. However, recent work with a genetically engineered strain has convincingly shown that the protease is not necessary for intracellular survival or virulence. As might be expected with a complex process like intracellular parasitism, it appears that the capability of Legionella strains to invade and multiply in host phagocytes is multifactorial and that no single moiety which is responsible for the virulence phenotype will be found.
 ...
PMID:Virulence factors of the family Legionellaceae. 157 12

To examine one possible mechanism of damage to leucocytes and tissue cells in legionellosis, seven species of Legionella were examined for cytolytic activity and for elaboration of phospholipase C, an enzyme that can damage mammalian cell membranes. Cytolysis was assessed using erythrocytes in agar. Phospholipase C was assayed by release of p-nitrophenol from p-nitrophenylphosphorylcholine and of tritiated phosphorylcholine from L-alpha-dipalmitoyl-[choline-methyl-3H]phosphatidylcholine. L. pneumophila, L. bozemanii, L. micdadei, L. dumoffii, L. gormanii, L. longbeachae and L. jordanis all lysed dog red blood cells, which have a high ratio of membrane phosphatidylcholine to sphingomyelin. The same strains hydrolysed varying amounts of p-nitrophenylphosphorylcholine; L. bozemanii exhibited the greatest activity. L. pneumophila, L. bozemanii, L. dumoffii, L. longbeachae and L. jordanis, but not L. micdadei, released tritiated phosphorylcholine from labelled substrate. These results indicate that several species of Legionella possess cytolytic capability; exotoxins with activity may play a role.
 ...
PMID:Cytolytic and phospholipase C activity in Legionella species. 404 20

Legionella pneumophila, the agent of Legionnaires' disease, is an intracellular parasite of aquatic protozoans and human macrophages. The type II protein secretion system of the Gram-negative Legionella organism promotes intracellular infection. A lipase activity and a p-nitrophenylphosphorylcholine (pNPPC) hydrolytic activity are two of the factors that are diminished in L. pneumophila type II secretion mutants. The Legionella lipase activity was found to include free fatty acid release from di- and triacylglycerol substrates, in addition to the previously reported cleavage of monoacylglycerol. In a number of other bacterial systems, the release of p-nitrophenol from pNPPC is due to a phospholipase C. In an attempt to identify exoproteins that potentiate intracellular infection, three genes were identified and mutated in L. pneumophila strain 130b that were predicted to encode either a secreted lipase or a phospholipase C. The first two genes, which were designated lipA and lipB, encoded proteins containing the lipase consensus sequence [LIV]-X-[LIVFY]-[LIVMST]-G-[HYWV]-S-X-G-[GSTAC]. Mutations in lipA in particular reduced supernatant activity against mono- and triacylglycerols. However, loss of lipA and/or lipB did not impair the ability of L. pneumophila to infect Hartmannella amoebae or U937 cell macrophages. The third L. pneumophila gene, which was denoted plcA, encoded a protein that was highly homologous with a phospholipase C from Pseudomonas fluorescens. Inactivation of plcA diminished secreted pNPPC hydrolase activity but did not influence Legionella infection of host cells. Taken together, these data indicate that L. pneumophila has multiple lipases and possibly several phospholipase C enzymes but that LipA, LipB and PlcA are not among those exoproteins required for optimal intracellular infection.
 ...
PMID:Legionella pneumophila genes that encode lipase and phospholipase C activities. 1210 9