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)

Legionella pneumophila is an intracellular parasite which is able to survive and multiply in human monocytes and alveolar macrophages. The Mip (macrophage infectivity potentiator) protein has been shown to be an essential virulence factor. A search of translated nucleic acid data bases has shown that the Mip protein from strain Wadsworth possesses regions homologous to those found in the FK506-binding proteins (FKBPs) of several different eukaryotic organisms. FKBPs are able to bind to the immunosuppressant macrolide FK506 and possess peptidyl-prolyl cis/trans isomerase (PPIase) activity. The gene coding for the Mip protein was cloned from the chromosome of L. pneumophila strain Philadelphia I and sequenced. It was synthesized in Escherichia coli K-12 and after purification it exhibited PPIase activity catalysing the slow cis/trans isomerization of prolyl peptide bonds in oligopeptides. Mip is inhibited by FK506 and fully resistant to cyclosporin A, as was also found for the recently characterized FKBP-type PPIases of eukaryotes. However, the N-terminal extension of Mip and/or the substitutions of the variable amino acids in the C-terminal FKBP core leads to variations, when compared with eukaryotic FKBPs, in substrate specificity with the oligopeptide substrates of type Suc-Ala-Xaa-Pro-Phe-4-nitroanilide. Nevertheless, the Legionella Mip factor represents a bacterial gene product which shares some characteristics normally found in eukaryotic proteins. In view of the activity of PPIases in protein-folding reactions, such prokaryotic FKBP analogues may represent a new class of bacterial pathogenicity factors.
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PMID:Mip protein of Legionella pneumophila exhibits peptidyl-prolyl-cis/trans isomerase (PPlase) activity. 137 19

A 27 kDa Chlamydia trachomatis Mip-like protein with homology of a 175-amino-acid C-terminal fragment to the surface-exposed Legionella pneumophila mip-gene product has previously been described. In this paper the entire chlamydia Mip-like sequence of C. trachomatis serovar L2 (lymphogranuloma venereum (LGV) biovar) is presented. The sequence shows high similarity to the legionella Mip protein and its C-terminal region, like that of the legionella Mip, has high amino acid similarity to eukaryotic and prokaryotic FK506-binding proteins. The chlamydial mip-like gene was detected by polymerase chain reaction (PCR) in other C. trachomatis serovars and by sequencing of the mip-like genes of serovars B and E (trachoma biovar) was shown to be highly conserved within the two major biovars of C. trachomatis. Monoclonal and polyclonal antibodies raised against the recombinant Mip-like protein failed to demonstrate surface-exposed epitopes on infectious elementary bodies or reproductive reticulate body forms either by immunofluorescence or immuno-gold electron microscopy. However, a complement-dependent inhibition of up to 91% of infectivity for cell cultures was observed with antibodies to the N-terminal fragment of the Mip-like protein suggesting that antibody-accessible epitopes are present on infectious EBs.
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PMID:Chlamydia trachomatis Mip-like protein. 140 89

Legionella pneumophila is an intracellular parasite of freshwater protozoa and human macrophages. Recent studies determined that the macrophage infectivity potentiator (Mip) surface protein, a prokaryotic homolog of the FK506-binding proteins, is required for optimal infection of macrophages. To determine whether Mip is also involved in L. pneumophila infection of protozoa, we examined the ability of a strain lacking Mip to parasitize Hartmannella amoebae and Tetrahymena ciliates. After 3 days of incubation, approximately 1000-fold fewer bacteria were recovered from protozoan cocultures infected with the Mip- strain than from those cocultures infected with an isogenic Mip+ strain. The mip mutant was, however, not impaired in its ability to bind to amoebae cell surfaces, indicating that Mip is involved in bacterial resistance to intracellular killing and/or intracellular multiplication. These data suggest that L. pneumophila employs similar genes and mechanisms to infect human cells and protozoa. Furthermore, they support the hypothesis that the ability of L. pneumophila to parasitize macrophages and hence to cause human disease is a consequence of its prior adaptation to intracellular growth within protozoa.
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PMID:Legionella pneumophila mip gene potentiates intracellular infection of protozoa and human macrophages. 159 30

Slow protein-folding reactions are accelerated by a prolyl cis/trans isomerase isolated from porcine kidney which is identical to cyclophilin, a protein that is probably the cellular receptor for the immunosuppressant cyclosporin A. Catalysis probably involves the isomerization of prolyl peptide bonds in the folding protein chains. Cyclosporin A inhibits folding catalysis by cyclophilin. Here we report the isolation, cloning, sequencing and expression of another protein with prolyl isomerase activity from Neurospora crassa which is unrelated to cyclophilin and which also catalyses slow steps in protein folding. This protein does, however, show sequence similarity to a human protein that binds to another, recently discovered immunosuppressive drug, FK506. Moreover, it shares 39% identity with the carboxy-terminal 114 residues of a cell-surface protein from the bacterium Legionella pneumophila, the causative agent of Legionnaires' disease. Catalysis of folding by the FK506-binding protein from N. crassa is inhibited by FK506, but not by cyclosporin A. Thus, at least two different classes of conformationally active enzymes (conformases) exist that catalyse slow steps in protein folding. Both occur in a wide variety of cells and are inhibited by immunosuppressive drugs.
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PMID:Isolation and sequence of an FK506-binding protein from N. crassa which catalyses protein folding. 169 87

After the demonstration of analogs of the Legionella pneumophila macrophage infectivity potentiator (Mip) protein in other Legionella species, the Legionella micdadei mip gene was cloned and expressed in Escherichia coli. DNA sequence analysis of the L. micdadei mip gene contained in the plasmid pBA6004 revealed a high degree of homology (71%) to the L. pneumophila mip gene, with the predicted secondary structures of the two Mip proteins following the same pattern. Southern hybridization experiments, with the plasmid pBA6004 as the probe, suggested that the mip gene of L. micdadei has extensive homology with the mip-like genes of several Legionella species. Furthermore, amino acid sequence comparisons revealed significant homology to two eukaryotic proteins with isomerase activity (FK506-binding proteins).
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PMID:Nucleotide sequence analysis of the Legionella micdadei mip gene, encoding a 30-kilodalton analog of the Legionella pneumophila Mip protein. 184 May 77

The Mip ('macrophage infectivity potentiator') protein of Legionella pneumophila has been shown to be an essential virulence factor, exhibiting peptidyl-prolyl cis/trans isomerase (PPIase) activity that can be inhibited by the immunosuppressant FK506. The cloning and sequencing of mip genes from three different L. pneumophila strains revealed a single amino acid substitution which did not affect the isomerase property of the enzyme. Mip proteins isolated from two wild-type L. pneumophila strains and from two corresponding Escherichia coli K-12 recombinant clones derived from these strains exhibited identical enzymatic properties and the precursor proteins are processed at identical cleavage sites. The mature Mip proteins exist in an oligomeric form. Site-directed mutagenesis demonstrated that a substitution of an Asp residue at position 142 by a Leu residue affects PPIase activity of Mip.
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PMID:Characterization of Mip proteins of Legionella pneumophila. 751 6

The molecular mass of the native FK506-binding peptidyl-prolyl cis/trans isomerase (PPIase) FKBP25mem from Legionella pneumophila (Mip (macrophage infectivity potentiator) protein) was determined by two methods. By gel-permeation chromatography we found no indication of the presence of the monomeric enzyme. However, an oligomeric state with a molecular mass of about 62 kDa was detected. By cross-linking with dimethyl pimelimidate and subsequent SDS-PAGE of either the surface proteins of intact L. pneumophila cells or the purified recombinant FKBP25mem in solution, we observed an immunoreactive band indicative of a mass in the dimer range. In contrast to human recombinant FKBP12, the enzymatic activity of Legionella FKBP25men was strongly dependent on the protein concentration, pointing to a dimer as the most active species. However, the inhibition by FK506 yielded a nearly constant value of Ki of about 250 nM when measured in the same range of FKBP25mem concentration. These results may be explained by the fact that monomeric FKBP25mem has little, if any, influence on enzymatic activity when compared with the homodimer.
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PMID:A homodimer represents an active species of the peptidyl-prolyl cis/trans isomerase FKBP25mem from Legionella pneumophila. 752 84

Immunophilins are housekeeping proteins present in a wide variety of organisms. Members of two protein superfamilies, cyclophilins (Cyps) and FK506-binding proteins (FKBPs) belong to this class of immunophilins. Despite the fact that the amino acid sequences of Cyp and FKBPs do not exhibit noticeable homology to each other, proteins of both classes are able to ligate immunosuppressive peptide derivatives. Cyps form complexes with the cyclic undercapeptide cyclosporin A and FKBPs are able to bind FK506 as well as rapamycin, both of which have a pipecolyl bond within their structure. In a ligand-bound form, immunophilins interfere with signal transduction in T cells. In addition, immunophilins have peptidyl prolyl cis-trans isomerase (PPlase) activity and are able to accelerate the rate of conformational events in proline-containing polypeptides. Microorganisms produce proteins that exhibit extensive sequence homologies to cyclophilins and FKBPs of higher organisms and which have considerable PPlase catalytic activity. While cyclophilins seem to be present in most if not all microbial species investigated, FKBPs are produced by yeasts as well as by a number of pathogenic bacteria, such as Legionella pneumophila, Chlamydia trachomatis and Neisseria meningitidis. The Mip protein of L. pneumophila is a virulence factor that plays an essential role in the ability of the bacteria to survive and multiply in phagocytic cells. Some results are summarized on the structure and putative functions of immunophilins and place special emphasis on the contribution of these polypeptides to the virulence of pathogenic microorganisms.
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PMID:Immunophilins: structure-function relationship and possible role in microbial pathogenicity. 752 21

The Mip surface protein, a prokaryotic analog of the FK506-binding proteins, enhances the ability of Legionella pneumophila to infect macrophages and protozoa. Using mip-specific probes and low-stringency Southern hybridizations, we have detected DNA sequences homologous to mip within Coxiella burnetii and Rochalimaea quintana. Using specific anti-Mip antisera and immunoblot analysis, we also detected Mip-related proteins within these bacteria as well as within Rickettsia and Ehrlichia species. These data suggest that Mip-related proteins have broad significance for host-parasite interactions. However, they also indicate that care must be exercised when using mip probes or anti-Mip antibodies for the detection of Legionella organisms in water or clinical samples.
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PMID:Detection of mip-like sequences and Mip-related proteins within the family Rickettsiaceae. 753 5

Macrophage infectivity potentiators are membrane proteins described as virulence factors in bacterial intracellular parasites, such as Legionella and Chlamydia. These factors share amino acid homology to eukaryotic peptidyl-prolyl cis-trans isomerases that are inhibited by FK506, an inhibitor of signal transduction in mammalian cells with potent immunosuppressor activity. We report here the characterization of a protein released into the culture medium by the infective stage of the protozoan intracellular parasite Trypanosoma cruzi. The protein possesses a peptidyl-prolyl cis-trans isomerase activity that is inhibited by FK506 and its non-immunosuppressing derivative L-685,818. The corresponding gene presents sequence homology with bacterial macrophage infectivity potentiators. The addition of the protein, produced heterologously in Escherichia coli, to cultures of trypomastigotes and simian epithelial or HeLa cells enhances invasion of the mammalian cells by the parasites. Antibodies raised in mice against the T.cruzi isomerase greatly reduce infectivity. A similar reduction of infectivity is obtained by addition to the cultures of FK506 and L-685,818. We concluded that the T.cruzi isomerase is involved in cell invasion.
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PMID:Secretion by Trypanosoma cruzi of a peptidyl-prolyl cis-trans isomerase involved in cell infection. 754 Jan 35


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