Adenylyl-Cyclase Toxin from Bordetella pertussis

Hewlett, Erik L.; Gray, Mary C.

doi:10.1007/978-3-662-05971-5_20

Cited by 13 publications

(5 citation statements)

References 72 publications

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“…In a prospective study, in which swabs for PCR and culture were obtained simultaneously from 555 individuals with cough illness, the use of PCR increased the identification of B. pertussis infections by almost fourfold, from 28 to 111 (693). In a similar but larger study, Schmidt-Schläpfer et al (694) found a 2.6-fold increase 350 MATTOO AND CHERRY CLIN. MICROBIOL.…”

Section: Specific Diagnosis Of B Pertussis Infectionsmentioning

confidence: 97%

“…Interestingly, surface-bound CyaA does not appear to be responsible for host cell intoxication; a recent report demonstrates that intoxication requires close contact of live bacteria with target cells and active secretion of CyaA (292). CyaA can enter a variety of eukaryotic cell types (350). Once inside, CyaA is activated by calmodulin (830) and catalyzes the production of supraphysiologic amounts of cyclic AMP (cAMP) from ATP (89,163,164,321).…”

Section: Virulence Determinantsmentioning

confidence: 99%

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Molecular Pathogenesis, Epidemiology, and Clinical Manifestations of Respiratory Infections Due toBordetella pertussisand OtherBordetellaSubspecies

2005

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Bordetella respiratory infections are common in people (B. pertussis) and in animals (B. bronchiseptica). During the last two decades, much has been learned about the virulence determinants, pathogenesis, and immunity of Bordetella. Clinically, the full spectrum of disease due to B. pertussis infection is now understood, and infections in adolescents and adults are recognized as the reservoir for cyclic outbreaks of disease. DTaP vaccines, which are less reactogenic than DTP vaccines, are now in general use in many developed countries, and it is expected that the expansion of their use to adolescents and adults will have a significant impact on reducing pertussis and perhaps decrease the circulation of B. pertussis. Future studies should seek to determine the cause of the unique cough which is associated with Bordetella respiratory infections. It is also hoped that data gathered from molecular Bordetella research will lead to a new generation of DTaP vaccines which provide greater efficacy than is provided by today's vaccines

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Section: Specific Diagnosis Of B Pertussis Infectionsmentioning

confidence: 97%

Section: Virulence Determinantsmentioning

confidence: 99%

Molecular Pathogenesis, Epidemiology, and Clinical Manifestations of Respiratory Infections Due toBordetella pertussisand OtherBordetellaSubspecies

2005

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“…Several bacteria produce adenylate cyclases, which can enter host cells and catalyse the production of the ubiquitous second messenger, cyclic AMP (cAMP). This feature is the basis for their being designated ‘adenylate cyclase toxins (ACTs)’ and the most extensively characterized of these are produced by Bacillus anthracis and the Bordetella species, especially Bordetella pertussis (Ladant and Ullmann, 1999; Leppla, 1999; Hewlett and Gray, 2000; Vojtova et al ., 2006a).…”

Section: Introductionmentioning

confidence: 99%

Cell cycle arrest induced by the bacterial adenylate cyclase toxins from Bacillus anthracis and Bordetella pertussis

Gray

Hewlett²

2010

Cellular Microbiology

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Summary Bacillus anthracis Edema Toxin (ET) and Bordetella pertussis Adenylate Cyclase Toxin (ACT) enter host cells and produce cAMP. To understand the cellular consequences, we exposed J774 cells to these toxins at ng/ml (pM) concentrations, then followed cell number and changes in cell signaling pathways. Under these conditions, both toxins produce a concentration-dependent inhibition of cell proliferation without cytotoxicity. ET and ACT increase the proportion of cells in G1/G0 and reduce S-phase, such that a single addition of ET or ACT inhibits cell division for 3 to 6 days. Treatment with ET or ACT produces striking changes in proteins controlling cell cycle, including virtual elimination of phosphorylated ERK 1/2 and Cyclin D1 and increases in phospho-CREB and p27Kip1. Importantly, PD98059, a MEK inhibitor, elicits a comparable reduction in Cyclin D1 to that produced by the toxins and blocks proliferation. These data show that non-lethal concentrations of ET and ACT impose a prolonged block on the proliferation of J774 cells by impairment of the progression from G1/G0 to S-phase in a process involving cAMP-mediated increases in phospho-CREB and p27Kip1 and reductions in phospho-ERK 1/2 and Cyclin D1. This phenomenon represents a new mechanism by which these toxins affect host cells.

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“…Thus the mechanisms of regulation of insulin transcription by glucose and glucagon-like polypeptide-1 (GLP-1), a candidate therapeutic agent for Type II diabetes [25], are still not established. Adenylate cyclase toxin (ACT) is a single polypeptide molecule produced by Bordetella pertussis [26,27]. It is present predominantly in an extracytoplasmic location in the bacterium.…”

Section: Introductionmentioning

confidence: 99%

“…It is present predominantly in an extracytoplasmic location in the bacterium. ACT enters target cells and catalyses the production of cAMP, and thus activates PKA [26,27]. The aims of the present study were to use this pharmacological agent to investigate the mechanisms by which physiological agents stimulate insulin secretion.…”

Section: Introductionmentioning

confidence: 99%

Protein kinase A translocation and insulin secretion in pancreatic β-cells: studies with adenylate cyclase toxin from Bordetella pertussis

Gao

Young

Trucco

et al. 2002

Biochemical Journal

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Activation of protein kinase A (cAMP-dependent protein kinase; PKA) triggers insulin secretion in the beta-cell. Adenylate cyclase toxin (ACT), a bacterial exotoxin with adenylate cyclase activity, and forskolin, an activator of adenylate cyclase, both dose-dependently increased insulin secretion in the presence, but not the absence, of glucose in insulin-secreting betaTC3 cells. The stimulation of cAMP release by either agent was dose-dependent but glucose-independent. Omission of extracellular Ca(2+) totally abolished the effects of ACT on insulin secretion and cytosolic cAMP accumulation. ACT and forskolin caused rapid and dramatic increases in cytosolic Ca(2+), which were blocked by nifedipine and the omission of extracellular Ca(2+). Omission of glucose completely blocked the effects of forskolin and partially blocked the effects of ACT on cytosolic Ca(2+). PKA alpha, beta and gamma catalytic subunits (Calpha, Cbeta and Cgamma respectively) were identified in betaTC6 cells by confocal microscopy. Glucose and glucagon-like polypeptide-1 (GLP-1) caused translocation of Calpha to the nucleus and of Cbeta to the plasma membrane and the nucleus, but did not affect the distribution of Cgamma. In conclusion, glucose and GLP-1 amplify insulin secretion via cAMP production and PKAbeta activation.

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Adenylyl-Cyclase Toxin from Bordetella pertussis

Cited by 13 publications

References 72 publications

Molecular Pathogenesis, Epidemiology, and Clinical Manifestations of Respiratory Infections Due toBordetella pertussisand OtherBordetellaSubspecies

Molecular Pathogenesis, Epidemiology, and Clinical Manifestations of Respiratory Infections Due toBordetella pertussisand OtherBordetellaSubspecies

Cell cycle arrest induced by the bacterial adenylate cyclase toxins from Bacillus anthracis and Bordetella pertussis

Protein kinase A translocation and insulin secretion in pancreatic β-cells: studies with adenylate cyclase toxin from Bordetella pertussis

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