Bordetella Toxin

Pertussis toxin (from Bordetella pertussis) [70323-44-3J Mr 117,000. Purified by stepwise elution from 3 columns comprising Blue Sepharose, Phenyl Sepharose and hydroxylapatite, and SDS-PAGE [Svoboda et al. Anal Biochem 159 402 1986, Biochemistry 21 5516 79[Pg.557]

Pertussis toxin is produced by the bacterium Bordetella pertussis. It covalently modifies G-proteins of the G/Go family (transfer of a ADP-ribose moiety of NAD onto G-protein a-subunits). ADP-ribosylated G-proteins are arrested in their inactive state and, as a consequence, functionally uncoupled from their respective effectors. Examples for pertussis toxin-sensitive cellular responses include the hormonal inhibition of adenylyl cyclases, stimulation ofK+ channels, inhibition of Ca2+ channels and stimulation ofthe cGMP-phosphodiesterase in retinal rods. 

This material is hazardous through inhalation and penetration through broken skin. Specific signs and symptoms of exposure to this toxin have not been established or have not been published. However, the major symptoms associated with whooping cough, the disease caused by Bordetella pertussis, are related to the effects of this toxin. 

Bordetella pertussis Toxin Borer Sol Boroethane Boron Bromide Boron Chloride Boron Fluoride Boron Hydride Boron Tribromide Boron Trichloride Boron Trifluoride Botox... 

Sandros, J., Rozdzinski, E., Zheng, J., Cowburn, D., and Tuomanen, E. (1994). Lectin domains in the toxin of Bordetella pertussis Selectin mimicry linked to microbial pathogenesis. Glycoconj.. 11,501-506. 

Pertussis toxin is a protein secreted by the bacterium Bordetella pertussis which causes whooping cough. The toxin enters a cell where it also catalyses ADP-ribosylation of the a-subunit of G-protein. 

The toxins produced by Bordetella pertussis (pertussis toxin) and Vibrio cholerae (cholera toxin) modify functions of certain G proteins to produce their pathoiogicai effects. 

The observed adjuvanticity of Bordetella pertussis is largely attributable to the presence of pertussis toxin and lipopolysaccharide (LPS). LPS, a constituent of the cell envelope of Gramnegative bacteria (Chapter 3), essentially consists of polysaccharide moieties to which lipid (lipid A) is covalently attached. 

The heat-labile E. coli enterotoxin, whose gene is carried on a plasmid, is a close relative of cholera toxin11 0 and also catalyzes ADP ribosylation of arginine 201 of the Gsa subunit.111 Bordetella pertussis, which causes whooping cough, forms a similar toxin that attacks the inhibitory regulatory protein G v as well as transducin and inactivates them by ADP ribosylation. Diphtheria toxin (Box 29-A), the exotoxin from Pseudomonas aeruginosa, and the toxin from Clostridium botulinum also catalyze ADP-ribosylation reactions.k/1 ... 

Jabbal-Gill, I., Fisher, A. N., Rappuoli, R., Davis, S. S., and Ilium, L. (1998), Stimulation of mucosal and systemic antibody responses against Bordetella pertussis filamentous haemagglutinin and recombinant pertussis toxin after nasal administration with chitosan in mice, Vaccine, 16,2039-2046. 

Fig. 2. Minimal components of the G protein-coupling cycle in a schematic chemotaxis pathway. (A) Chemotaxis G protein-coupled receptors reside in the plasma membrane associated with specific heterotrimeric G proteins. (B) Upon binding of a chemoattractant such as fMLF, the receptor catalyzes the exchange of GTP for GDP in the a subunit of the G protein, thereby dissociating the GTP-bound a subunit from the (3 subunit complex. Chemotaxis GPCRs typically utilize the a isoform of the a subunit. (C) Subsequently the dissociated GTP-bound a subunit and the j3 subunit complex each dock to effectors elsewhere in the cell. (D) The a subunit possesses intrinsic GTPase activity that hydrolyzes the bound GTP to GDP, thereby regenerating the GDP-bound Oj subunit that reassociates with the / 7 subunit complex and with the receptor. Bordetella pertussis toxin covalently and specifically modifies the isoform of the a subunit and prevents its association with receptor (see text for additional discussion and references).

Some of the G rroteins are substrates for ADP-ribosylation by bacterial toxins. Specifically, toxins from Vibrio cholera, cholera toxin (CT) or Bordetella pertussis, pertussis toxin (PT), can covalently modify the G roteins by addition of an ADP-ribose... 

Whole-cell and acellular pertussis vaccines have been reviewed, with emphasis on the protectivity of the various virulence factors and antigens (1). The authors summarized their review as follows although Bordetella pertussis has at least five proteins required for virulence and an additional two toxic components, only serum neutralizing antibodies to pertussis toxin have been shown to confer immunity to pertussis. 

Arico B, Rappuoli R (1987) Bordetella parapertussis and Bordetella bronchiseptica contain transcriptionnally silent pertussis toxin genes. In J. Bacterial. 169 2847-2853. 

Baker SM, Masi A, Liu D-F, etal. (1995) Pertussis toxin export genes are regulated by the pfx promoter and may be required for efficient translation of pix mRNA in Bordetella pertussis. In Infect. Immun. 63 3920-3926. 

Boucher PE, Stibitz S (1995) Synergistic binding of RNA polymerase and BvgA phosphate to the pertussis toxin promoter of Bordetella pertussis. In J. Bacterial. 177 6486-6491. 

DeShazer D, Wood GE, Friedman RL (1995) Identification of a Bordetella pertussis regulatory factor required for transcription of the pertussis toxin operon in Escherichia coli. In J. Bacterial. 177 3801 -3807. 

Johnson FD, Bums DL (1994) Detection and subcellular localization of three PtI proteins involved in the secretion of pertussis toxin from Bordetella pertussis. In J. Bacterial. 176 5350-5356. 

Kotob SI, Hausman SZ, Burns DL (1995) Localization of the promoter for the ptI genes in Bordetella pertussis, which encode proteins essential for secretion of pertussis toxin. In Infect. Immun. 63 3227-3230. 

Pertussis toxin is produced by certain Bordetella pertussis strains, which are pathogenic organisms (Yajima et al., 1978a,b). Since the toxin is commercially available in adequate quality we do not purify PT from cultured 6. pertussis. Those who are interested in culturing 6. pertussis and purifying PT are referred to detailed laboratory protocols published previously (Sekura, 1985). 

Moss J, Stanley SJ, Watkins PA et al. (1986) Stimulation of the thiol-dependent ADP-ribosyltransferase and NAD glycohydrolase activities of Bordetella pertussis toxin by adenine nucleotides, phospholipids, and detergents. In Biochemistry 25 2720-2725... 

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