Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bordetella pertussis, the causative agent of whooping cough, adheres to human monocytes/macrophages by means of a bacterial surface-associated protein, filamentous hemagglutinin (FHA) and the leukocyte integrin, complement receptor 3 (CR3, alpha M beta 2, CD11b/CD18). We show that an FHA Arg-Gly-Asp site induces enhanced B. pertussis binding to monocytes, and that this enhancement is blocked by antibodies directed against CR3. Enhancement requires a monocyte signal transduction complex, composed of leukocyte response integrin (alpha? beta 3) and integrin-associated protein (CD47). This complex is known to upregulate CR3 binding activity. Thus, a bacterial pathogen enhances its own attachment to host cells by coopting a host cell signaling pathway.
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PMID:Bordetella pertussis filamentous hemagglutinin interacts with a leukocyte signal transduction complex and stimulates bacterial adherence to monocyte CR3 (CD11b/CD18). 793 Oct 59

We characterized the endothelin (ET) receptor subtypes responsible for signal transduction in cultured porcine kidney epithelial LLC-PK1 cells. Both ET-1 (IC50, 43 pM) and ET-3 (IC50, 46 pM) inhibited the binding of [125I]ET-1 to LLC-PK1 cells to a similar extent. The binding affinity of LLC-PK1 cells was about 10,000 times higher for the ETB antagonist BQ-788 [N-cis-2,6-dimethyl-piperidinocarbonyl-L-tau-metylleucyl-D-+ ++Nin- methoxycarbonyltryptophanyl-D-norleucine] (IC50, 1.3 nM) than for the ETA antagonist BQ-123 [cyclo-(D-Trp-D-Asp-Pro-D-Val-Leu)] (IC50, 14 microM). ET-1 enhanced cyclic GMP (cGMP) production, but reduced vasopressin- and forskolin-stimulated cyclic AMP (cAMP) production. Both effects of ET-1 were antagonized by BQ-788, but not by BQ-123. The cAMP decrease, but not the cGMP increase, in response to ET-1 was inhibited by pertussis toxin, suggesting that the former response is mediated by pertussis toxin-sensitive Gi, whereas the latter is mediated by a pertussis toxin-insensitive G-protein. Therefore, the ETB receptors in LLC-PK1 cells couple to the two types of signal transduction cascades to reduce cAMP production and stimulate cGMP production via distinct G-proteins. ET-1 and probably also ET-3 may play a role in the regulation of renal epithelial transport by decreasing cAMP and increasing cGMP.
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PMID:Endothelin ETB receptors couple to two distinct signaling pathways in porcine kidney epithelial LLC-PK1 cells. 793 50

The 1706-residue adenylate cyclase toxin (CyaA) of Bordetella pertussis is an RTX protein with extensive carboxy-proximal glycine and aspartate-rich repeats. CyaA does not have a cleavable amino-terminal signal peptide and can be secreted across both bacterial membranes of the Escherichia coli cell envelope by the alpha-haemolysin (HlyA) translocator (HlyBD/TolC). We performed deletion mapping of secretion signals recognized in CyaA by this heterologous translocator. Truncated proteins with N-terminal and internal deletions were secreted at levels up to 10 times higher than intact CyaA and similar to HlyA. A secretion signal recognized by HlyBD/TolC was found within the last 74 residues of CyaA. However, secretion of CyaA was reduced but not abolished upon deletion of the last 75 or 217 residues, indicating that at least two additional secretion signals recognized by HlyBD/TolC are within CyaA. One of them was localized to the repeat sequence between residues Asp-1587 to Ile-1631. Interestingly, a conserved 'acidic' motif (Glu/Asp)-(X)11-Asp-(X)3/5-(Glu/Asp)-(X)14-Asp was found in the C-terminal sequences of HlyA, CyaA and the two secreted CyaA derivatives. We speculate that the presence and spacing of acidic residues may be an important feature of secretion signals recognized by the haemolysin translocator.
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PMID:Repeat sequences in the Bordetella pertussis adenylate cyclase toxin can be recognized as alternative carboxy-proximal secretion signals by the Escherichia coli alpha-haemolysin translocator. 793 26

cDNAs coding for three types of alpha-subunits of GTP-binding proteins Gs and G0 (a short form of alpha s with Asp-Ser in positions 71 and 72, a long form of alpha s with the insertion of 16 amino acid residues instead of Asp-Ser (71-72)--both from bovine brain, and alpha 0 from bovine cerebellum as well as some chimeric alpha s/alpha 0 genes were cloned into a modified pGEM-2 plasmid vector under the control of the SP6 promoter. All the genes were in vitro transcribed and translated, and some functional properties of the resulting proteins were determined, such as adenylyl cyclase activation, ADP-ribosylation with pertussis toxin, limited nucleotide-dependent trypsin proteolysis. Parts of the alpha s polypeptide chain necessary for the activation of adenylyl cyclase were mapped. The alpha s domain interacting with adenylyl cyclase is formed by the alpha s polypeptide chain fragments 235-294 and 337-356 (numbering as of the alpha s long form).
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PMID:[Localization of segments in the Gs protein interacting with adenylate cyclase using a Gs/G0-chimera]. 811 36

Intracellular Ca2+ responses to extracellular matrix molecules were studied in suspensions of pancreatic acinar cells loaded with Fura-2. Collagen type I, laminin, fibrinogen and fibronectin were unable to raise cytosolic free Ca2+ concentration ([Ca2+]i), whereas collagen type IV, at concentrations from 5 to 50 micrograms/ml, significantly increased it. The effect of collagen type IV was not due to possible contamination with type-I transforming growth factor beta or plasminogen, as neither of these agents was able to increase [Ca2+]i. Using highly specific mass assays, concentrations of inositol lipids, 1,2-diacylglycerol (DAG) and Ins(1,4,5) P3 were measured in pancreatic acinar cells stimulated with collagen type IV. A decrease in the concentrations of PtdIns(4,5) P2 and PtdIns4 P with a concomitant increase in the concentrations of DAG and InsP3 mass were observed, showing that collagen type IV increases [Ca2+]i by activation of phospholipase C. The observed [Ca2+]i signals had two components, the first resulting from Ca2+ release from the intracellular stores, and the second resulting from Ca2+ flux from the extracellular medium through the verapamil-insensitive channels. A tyrosine kinase inhibitor (tyrphostine) was able to block inositol lipid signalling caused by collagen type IV, which together with the insensitivity of this pathway to cholera toxin and pertussis toxin or to preactivation of protein kinase C, the longer duration of the increase in [Ca2+]i and a longer lag period needed for observation of increases in DAG and InsP3 concentration with collagen type IV than with carbachol (50 mM) suggest that activation of phospholipase C by collagen type IV is caused by tyrosine kinase activation. Inositol lipid signalling and increases in [Ca2+]i were also observed with Arg-Gly-Asp (RGD)-containing peptide but not with Arg-Asp-Gly (RDG)-containing peptide. Collagen type IV and RGD-containing peptide, but not carbachol, competed in increasing [Ca2+]i and DAG concentration, suggesting that the binding site of collagen type IV responsible for phospholipase C activation contains the RGD sequence. Together the present results suggest that, in pancreatic acinar cells, RGD sequence(s) within collagen type IV molecules cause activation of tyrosine kinase, probably through one of the integrin receptors, which then stimulates phospholipase C and increases [Ca2+]i.
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PMID:Collagen type IV stimulates an increase in intracellular Ca2+ in pancreatic acinar cells via activation of phospholipase C. 819 49

We have purified CR3 to homogeneity by affinity chromatography on C3bi-Sepharose and elution with EDTA. C3bi-coated erythrocytes bound to this purified CR3, and binding was dependent on the concentration of both C3bi and CR3, as well as on temperature and the presence of divalent cations. Moreover, binding could be blocked by mAb against CR3 or C3bi and could be enhanced by the addition of integrin modulating factor-1. We used the purified CR3 to test whether several putative ligands of CR3 directly bound the receptor. The interaction of purified CR3 with fibrinogen, filamentous hemagglutinin of Bordetella pertussis, lipophosphoglycan and glycoprotein 63 of Leishmania mexicana, and lipopolysaccharide from Escherichia coli was confirmed. However the interaction of CR3 with zymosan or its major component, beta-glucan, was not observed in these assays. Previous studies showed that binding of C3bi to PMN could be blocked with Arg-Gly-Asp (RGD) containing peptides and were interpreted to indicate that the RGD sequence in C3bi interacts directly with CR3. We found, however, that RGD containing peptides were unable to block the interaction of C3bi with purified CR3, yet retained the ability to block binding of C3bi to cells. We conclude that RGD-peptides do not directly bind CR3, but instead indirectly effect CR3 function. Inasmuch as the effect of RGD-peptides could be mimicked with antibodies against leukocyte response integrin, we suggest that RGD-peptides may bind to leukocyte response integrin on polymorphonuclear leukocytes and influence CR3 activity via this receptor.
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PMID:Ligand specificity of purified complement receptor type three (CD11b/CD18, alpha m beta 2, Mac-1). Indirect effects of an Arg-Gly-Asp (RGD) sequence. 837 80

Bordetella pertussis, the human pathogen of whooping cough, when grown at 22 degrees C is nonvirulent and unable to bind eukaryotic cells. In response to a temperature shift to 37 degrees C, the bacterium acquires the ability to bind eukaryotic cells in a time-dependent fashion. By studying in vitro the temperature-induced transition, from the nonvirulent to the virulent state, we found that binding to CHO cells is mediated by the Arg-Gly-Asp-containing domain of filamentous hemagglutinin (FHA), a protein with multiple binding specificities. This protein is synthesized as a 367-kDa polypeptide within 10 min after temperature shift, but requires 2 hr before it is detected on the bacterial cell surface and starts to bind CHO cells. Mutations affecting the cell surface export of FHA abolish bacterial adhesion to CHO cells, while mutations in the outer membrane protein pertactin strongly reduce binding. This suggests that multiple chaperon proteins are required for a correct function of FHA. Finally, several hours after maximum binding efficiency is achieved, the N-terminal 220-kDa portion of FHA that contains the binding regions is cleaved off, possibly to release the bacteria from the bound cells and facilitate spreading. The different forms of FHA may play different roles during bacterial infection.
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PMID:Adhesion of Bordetella pertussis to eukaryotic cells requires a time-dependent export and maturation of filamentous hemagglutinin. 841 78

The composition of the peptidoglycan of Haemophilus influenzae was determined by analyzing glycopeptides generated by M1 muramidase hydrolysis using high pressure liquid chromatography, fast atom bombardment mass spectrometry, and fast atom bombardment collisionally activated dissociation tandem mass spectrometry, and amino acid analysis. The structures of 17 glycopeptides, representing 96% of the total peptidoglycan, were ascertained. Fifteen glycopeptides resembled species described for Escherichia coli peptidoglycan (Glauner, B., and Schwarz, U. (1983) The Target of Penicillin (Hackenbeck, R., ed), Walter de Gruyter, Berlin pp. 29-34) as compared with 9 in common with Bordetella pertussis (Tuomanen, E., Schwartz, J., Sande, S., Light, K., and Gage, D. (1989) J. Biol. Chem. 264, 11093-11098). Substitutions for L-alanine in the fourth position of the stem peptide included glycine, aspartic acid, and serine. The peptidoglycan was 27% cross-linked, 2% of which formed between diaminopimelic acid residues. No species was identified containing lysyl-arginine residues characteristic of lipoprotein. The peptidoglycan of non-beta-lactamase-mediated antibiotic-resistant H. influenzae differed from that of sensitive strains by an increase in the amount of disaccharide tripeptides and a decrease in 1,6-anhydro dimers. Both changes were transformable properties that changed in a stepwise fashion in parallel with the degree of antibiotic resistance.
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PMID:Composition of the peptidoglycan of Haemophilus influenzae. 850 90

To investigate the action of endothelin-1 (ET-1) on L-type Ca currents (ICa,L) in guinea-pig ventricular cells, whole-cell currents were recorded at approximately 36-37 degrees C in enzymatically isolated myocytes. ET-1 (> or =10 nM) suppressed the basal ICa,L to 79+/-8% of control at 20 nM. Bath application of isoproterenol (ISO; 10 nM) enhanced ICa,L to 192+/-28% with about a -10-mV shift of its relationship with membrane potential. ET-1 concentration dependently inhibited this ISO-enhanced ICa,L with a half-maximally inhibitory concentration (IC50) of 168 pM. The inhibitory actions of ET-1 were antagonised by BQ-123 (300 nM), cyclo(D-Asp-L-Pro-D-Val-L-Leu-D-Trp), a specific ETA receptor antagonist. Histamine-enhanced ICa,L was also suppressed by ET-1, but ICa, L potentiated by internal adenosine 3',5'-cyclic monophosphate (cAMP) was unaffected. Preincubation of myocytes with pertussis toxin (PTX, at 5 microgram/ml for >60 min at 36 degrees C) completely occluded the ET-1 action. Thus, stimulation of ETA receptors by subnanomolar ET-1 inhibits ICa,L via PTX-sensitive G-proteins.
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PMID:Endothelin-1 inhibits L-type Ca currents enhanced by isoproterenol in guinea-pig ventricular myocytes. 859 96

The active site of the enzymatic component (Ia) of the Clostridium perfringens iota toxin has been studied by site-directed mutagenesis. Sequence alignment showed that Ia and C3 enzymes display a segment in their C-terminal part which is homologous to that forming the active domain of pertussis toxin, cholera toxin, and Escherichia coli thermolabile toxins. This structure consists of a beta-strand and an alpha-helix which forms the NAD-binding cavity and which is flanked by two catalytic spatially conserved residues involved in catalysis [Domenighini et al. (1994) Mol. Microbiol. 14, 41-50]. Substitutions (Arg-295-Lys, Glu-378-Ala, Glu-380-Asp, and Glu-380-Ala) induced a drastic decrease in ADP-ribosylation and cytotoxic activities, while substitution of the adjacent Arg (Arg-296-Lys) only partially affected the enzymatic activity and cytotoxicity. These results indicate that Arg-295, Glu-378 and Glu-380 of Ia are involved in the ADP-ribosylation activity which is essential for the morphological changes of cells treated with iota toxin.
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PMID:Evidence that Arg-295, Glu-378, and Glu-380 are active-site residues of the ADP-ribosyltransferase activity of iota toxin. 889 93


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