Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two toxins from Bordetella pertussis, pertussis toxin and Bordetella adenylate cyclase, cause profound disruptions of cAMP metabolism in mammalian cells. While the role of each toxin in the whooping cough syndrome is unknown, it is highly likely that together they confer on the organism an important proliferative advantage. Intact B. pertussis cells express large amounts of adenylate cyclase activity on their exterior surface. In a presently unknown fashion, this enzyme can enter human phagocytes, elevate cellular cAMP and impair host defense. We reasoned that this unusual enzyme might serve to signal the presence of B. pertussis in nasopharyngeal swabs from infected persons. Here we report a series of in vitro experiments which confirm the feasibility of such an approach. We find that calcium alginate swabs containing as few as 100 B. pertussis organisms produce readily detectable amounts of cAMP in our assay. Nasopharyngeal secretions swabbed from healthy volunteers, however produced no detectable cAMP alone and did not affect the production of cAMP by B. pertussis. We have also tested pure cultures of four common bacterial pathogens (Haemophilus influenzae, Streptococcus pyogenes, Staphylococcus aureus, and Escherichia coli) which may be co-isolated in clinical whooping cough and find that none interferes with the detection of B. pertussis. We conclude that the unique adenylate cyclase of B. pertussis might be a valuable diagnostic device.
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PMID:Bordetella adenylate cyclase: host toxicity and diagnostic utility. 287 18

Varying dietary linoleic acid altered lung membrane fatty acid composition with linoleic acid content increasing from approximately 6% total in those on 3 en% diet to approximately 14% total fatty acid in those on a 12 en% diet. Accompanying this were two- to three-fold increases in the levels of the elongation products of linoleic acid, namely 20:2 (n-6) and 22:5 (n-6) and a decrease in 18:1 oleic acid from approximately 26% to approximately 19% total. Administration of Haemophilus influenzae, to animals on 6 en% linoleic acid, serving as a model for atopy, effected a small increase in the levels of 22:5 (n-3) and doubled those of 22:6 (n-3). beta-Adrenergic-induced tracheal relaxation and stimulation of lung adenylate cyclase were elevated by increasing dietary linoleic acid from 3 to 6 en%, although such differences were abolished in the atopic model and when dietary linoleic acid was increased to 12 en%. Arrhenius plots of NaF-stimulated lung adenylate cyclase activities exhibited a break (t1) at approximately 26 degrees C in all dietary groups with unchanged activation energies and activity. In contrast, whilst both isoprenaline and PGE2-stimulated adenylate cyclase activities showed similar break-points in their Arrhenius plots, dietary linoleic acid manipulation markedly altered their form. As with NaF-stimulated activities then, irrespective of dietary manipulation and induction of atopy, these plots showed an invariant break occurring at approximately 26 degrees C. But, for animals on 3 and 6 en% diets, a second break was apparent at approximately 15 degrees C, which was slightly decreased to approximately 12 degrees C upon induction of atopy and completely abolished on increasing dietary linoleic acid to 12 en%. Accompanying such changes were marked alterations in activation energies. We suggest that profound changes in lung plasma membrane bilayer properties occur upon both altering dietary linoleic acid levels and in atopy. These selectively perturb adenylate cyclase activity when it is receptor-stimulated but not when it is activated by direct G-protein stimulation with NaF. We suggest that atopy and dietary challenge elicit an asymmetric perturbation of the plasma membrane that predominantly affects the outer half of the lipid bilayer.
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PMID:Dietary linoleic acid-induced changes in respiratory beta-adrenergic receptor function and the form of arrhenius plots of isoprenaline- and prostaglandin E2-stimulated adenylate cyclase activity in a model for atopy. 808 82

Competence for transformation in Haemophilus influenzae is stimulated by cyclic AMP (cAMP) and requires the cAMP-dependent catabolite regulatory protein CRP. Thus, understanding the control of competence will require understanding how cAMP levels are regulated. As a first step, we have cloned the H. influenzae adenylate cyclase gene (cya) by complementing the Lac- phenotype of delta cya Escherichia coli. Its sequence specifies an 843-amino-acid protein which has significant identity to other known bacterial adenylate cyclases (41 to 43% and 61% identical to the cya genes of enteric bacteria and of Pasteurella multocida, respectively). As seen in other bacterial cya genes, there is evidence for regulation similar to that demonstrated for E. coli: the presence of a strong consensus CRP binding site within the promoter of the gene may provide feedback control of cAMP levels by repressing cya transcription, and translation may be limited by the weak ribosome binding site and by initiation of protein synthesis with GUG rather than AUG or the UUG used in other bacterial cya genes. We confirmed the essential role of cAMP in competence by constructing and characterizing H. influenzae cya mutants. This strain failed to develop competence either spontaneously or after transfer to a competence-inducing medium. However, it became as competent as its wild-type parent in the presence of exogenous cAMP. This result suggests that the failure of exogenously added cAMP to induce optimum competence in wild-type cells is not due to a limitation to the entry of cAMP into the cells. Rather, it strongly favors models in which competence induction requires both an increase in intracellular cAMP and a second as yet unidentified regulatory event. H. influenzae strains mutant in cya or crp were unable to ferment xylose or ribose. This confirms that influenzae, like E. coli, uses cAMP and CRP to regulate nutrient uptake and utilization and lends increasing support to the hypothesis that DNA uptake is mechanism of nutrient acquisition.
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PMID:The Haemophilus influenzae adenylate cyclase gene: cloning, sequence, and essential role in competence. 822 61

Haemophilus influenzae Rd becomes competent for transformation by nutritional downshift or transient anaerobic growth through a process that requires cyclic AMP receptor protein and adenylate cyclase. Insertion mutations in crr or ptsI of the phosphoenolpyruvate:carbohydrate phosphotransferase system lowered transformation frequencies, and the effect was reversed by the addition of cyclic AMP. However, insertions into H. influenzae homologs of two-component signal transduction genes had no effect on competence.
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PMID:Role of the two-component signal transduction and the phosphoenolpyruvate: carbohydrate phosphotransferase systems in competence development of Haemophilus influenzae Rd. 889 43