Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Legionnaire's disease bacterium, Legionella pneumophila, is a facultative intracellular pathogen which invades and replicates within two evolutionarily distant hosts, free-living protozoa and mammalian cells. Invasion and intracellular replication within protozoa are thought to be major factors in the transmission of Legionnaire's disease. Although attachment and invasion of human macrophages by L. pneumophila is mediated in part by the complement receptors CR1 and CR3, the protozoan receptor involved in bacterial attachment and invasion has not been identified. To define the molecular events involved in invasion of protozoa by L. pneumophila, we examined the role of protein tyrosine phosphorylation of the protozoan host Hartmannella vermiformis upon attachment and invasion by L. pneumophila. Bacterial attachment and invasion were associated with a time-dependent tyrosine dephosphorylation of multiple host cell proteins. This host cell response was highly specific for live L. pneumophila, required contact with viable bacteria, and was completely reversible following washing off the bacteria from the host cell surface. Tyrosine dephosphorylation of host proteins was blocked by a tyrosine phosphatase inhibitor but not by tyrosine kinase inhibitors. One of the tyrosine dephosphorylated proteins was identified as the 170-kD galactose/N-acetylgalactosamine-inhibitable lectin (Gal/GalNAc) using immunoprecipitation and immunoblotting by antibodies generated against the Gal/GalNAc lectin of the protozoan Entamoeba histolytica. This Gal/GalNAc-inhibitable lectin has been shown previously to mediate adherence of E. histolytica to mammalian epithelial cells. Uptake of L. pneumophila by H. vermiformis was specifically inhibited by two monovalent sugars, Gal and GalNAc, and by mABs generated against the 170-kD lectin of E. histolytica. Interestingly, inhibition of invasion by Gal and GalNAc was associated with inhibition of bacterial-induced tyrosine dephosphorylation of H. vermiformis proteins. High stringency DNA hybridization confirmed the presence of the 170-kD lectin gene in H. vermiformis. We conclude that attachment of L. pneumophila to the H. vermiformis 170-kD lectin is required for invasion and is associated with tyrosine dephosphorylation of the Gal lectin and other host proteins. This is the first demonstration of a potential receptor used by L. pneumophila to invade protozoa.
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PMID:Identification of a Gal/GalNAc lectin in the protozoan Hartmannella vermiformis as a potential receptor for attachment and invasion by the Legionnaires' disease bacterium. 925 52

Legionella pneumophila causes Legionnaires' disease by replication in alveolar macrophages and monocytes. The bacteria are internalized most efficiently by opsonin-dependent, CR3-mediated phagocytosis. This investigation focused on determining the role of actin polymerization and phosphorylation signals in this uptake mechanism. Uptake inhibition assays and confocal microscopic analysis indicated that entry of L. pneumophila activated tyrosine kinase (TK) and protein kinase C (PKC) and induced actin polymerization at the site of bacterial entry. Upon L. pneumophila entry, six major cellular proteins (75, 71, 59, 56, 53, and 52 kDa) were TK phosphorylated in soluble fractions of monocytes, and three of these proteins (52, 53, and 56 kDa) were consistently found in insoluble (i.e., cytoskeletal) fractions of monocytes as well. Tyrosine phosphorylation was suppressed when cells were pretreated with the kinase inhibitor genistein, tyrphostin, or staurosporine. A similar tyrosine-phosphorylated protein pattern was observed with CR3-mediated entry of avirulent L. pneumophila, Escherichia coli, or zymosan into monocytes. This study has shown that PKC and TK signals which activate actin polymerization during the process of phagocytosis are induced upon L. pneumophila entry. In addition, CR3 receptor-mediated phagocytosis into monocytes may involve tyrosine phosphorylation of similar proteins, regardless of the particle being phagocytosed. Therefore, the tyrosine-induced phosphorylation observed during opsonized L. pneumophila entry is not a virulence-associated event.
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PMID:Signal transduction during Legionella pneumophila entry into human monocytes. 959 66

Intracellular replication of the Legionnaires' disease bacterium, Legionella pneumophila, within protozoa plays a major role in bacterial ecology and pathogenesis. Invasion of the protozoan host Hartmannella vermiformis by L. pneumophila is mediated by attachment to the Gal/GalNAc lectin receptor, which is similar to the beta(2) integrin transmembrane receptors of mammalian cells. Bacterial invasion is associated with induction of a protein tyrosine phosphatase (PTPase) activity in H. vermiformis that results in tyrosine dephosphorylation of the lectin receptor and several cytoskeletal proteins. In this report, we show that entry of L. pneumophila into H. vermiformis is not required to induce tyrosine dephosphorylation of one of the cytoskeletal proteins, paxillin. Tyrosine dephosphorylation of paxillin is mediated at the level of bacterial attachment to the lectin receptor, and is blocked by inhibiting bacterial attachment to the lectin receptor. Attachment of L. pneumophila to the lectin receptor is not mediated by the type IV pilus, which is one of the bacterial ligands involved in attachment to protozoa. Interestingly, the lectin receptor in resting H. vermiformis is associated with several phosphorylated proteins that are dissociated upon bacterial attachment and invasion. We show that the L. pneumophila-induced PTPase activity in H. vermiformis and the associated tyrosine dephosphorylation of host proteins can be mimicked by the cytoskeletal disrupting agent, cytochalasin D. Taken together, our data indicate that attachment of L. pneumophila to the lectin receptor of H. vermiformis induces a PTPase activity, tyrosine dephosphorylation of the lectin and cytoskeletal proteins, dissociation of the lectin from its associated phosphorylated proteins, and most probably disassembly of the cytoskeleton. This novel L. pneumophila-protozoa interaction may be a bacterial strategy to invade protozoa and to be trafficked into a replicative 'niche', or to block differentiation of the protozoan host into a cyst in which L. pneumophila cannot replicate.
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PMID:Signal transduction in the protozoan host Hartmannella vermiformis upon attachment to Legionella pneumophila. 1096 69

The Legionella pneumophila (Lp), human pathogen causes severe and often fatal Legionnaires' disease, produces a major virulence factor, termed 'macrophage infectivity potentiator protein' (Mip), that is necessary for optimal multiplication of the bacteria within human alveolar macrophages. Mip exhibits peptidyl prolyl cistrans isomerase (PPIase) activity, which can be inhibited by Rapamycin and FK506. Mutation of Mip protein on catalytic residues at Aspartate-142 position replaced to Leucine-142 and Tyrosine-185 position replaced to Alanine-185 that strongly reduces the PPIase activity. Therefore, we aim to develop an in-silico mutagenesis model for both important catalytic residues, validated the stability of the mutated model. Further, we have docked to the known inhibitor rapamycin with Lp Mip (native) and mutants (D142L and Y185A) to analyze the conformational and binding model. For electrostatic contributions and VanderWaals interactions are the major driving force for rapamycin binding and largely responsible for the binding differences between the Lp Mip (native and mutated) proteins.
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PMID:In silico analysis of conformational changes induced by normal and mutation of macrophage infectivity potentiator catalytic residues and its interactions with Rapamycin. 2566 11