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Gene Review

ccdB  -  plasmid maintenance protein CcdB

Salmonella enterica subsp. enterica serovar Typhimurium str. LT2

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Disease relevance of ccdB

  • The mechanism of salmonella activation of adenylate cyclase is unclear but apparently differs from that of cholera toxin in that it is inhibited by indomethacin [1].
  • Extracellular transport of cholera toxin B subunit using Neisseria IgA protease beta-domain: conformation-dependent outer membrane translocation [2].
  • A vector has been constructed to allow genetic fusions of guest antigens via a hinge domain to the C terminus of the highly immunogenic C fragment of tetanus toxin [3].
  • Toxin levels were diminished by purifying phage preparations [4].
  • Bacillus anthracis, the causative agent of anthrax, produces systemic shock and death in susceptible animals, primarily through the action of its lethal toxin [5].

High impact information on ccdB

  • Furthermore, all of the mice were solidly protected when challenged with lethal doses of either tetanus toxin or the virulent Salmonella typhimurium strain C5 [3].
  • Sensitivity could be restored by coinjection of toxin-sensitive cultured macrophages (RAW 264.7 cells) but not by coinjection of other cell lines tested [5].
  • This 1- to 3-kDa nominal molecular mass chemokine-like bioactivity directly stimulates PMN via a pertussis toxin-sensitive receptor and elicits a Ca2+ signal [6].
  • These findings, when taken together with results presented in the accompanying paper, strengthen the argument that bacterial toxin production (and the ability of the host to respond to the toxin) can represent a critical determinant of the induction of macrophage Ia expression and in turn, of Ag-specific T cell responses during bacterial infection [7].
  • One of the most likely candidates for the lethal toxin in salmonellosis is endotoxin, specifically the lipid A domain of the lipopolysaccharide (LPS) molecule [8].

Chemical compound and disease context of ccdB

  • Construction, expression, and immunogenicity of the Schistosoma mansoni P28 glutathione S-transferase as a genetic fusion to tetanus toxin fragment C in a live Aro attenuated vaccine strain of Salmonella [3].
  • Multiple tandem copies of an immunogenic epitope comprising amino acids 8-23 of glycoprotein D of herpes simplex virus (HSV) were expressed as C-terminal fusions to tetanus toxin fragment C (TetC) in different Salmonella typhimurium live vaccine strains [9].
  • Intraperitoneal administration of zinc (ZnIP) as zinc chloride prior to or simultaneously with a lethal quantity of intraperitoneally administered Salmonella typhimurium endotoxin significantly protected rats against toxin-induced mortality and hepatocellular damage [10].
  • The toxicity of six of these isolates could be attributed to the presence of citrinin, tenuazonic acid, or T-2 toxin [11].
  • Of the adsorbents tested, aluminum hydroxide showed a positive effect only with E. coli LT and A. hydrophila, while cholestyramine affected net fluid flux only with E. coli ST (heat-stable toxin) [12].

Biological context of ccdB


Anatomical context of ccdB


Associations of ccdB with chemical compounds


Regulatory relationships of ccdB


Other interactions of ccdB

  • We have previously described a new system for the delivery of recombinant antigens in live Salmonella vaccines as genetic fusions to the C terminus of fragment C of tetanus toxin (TetC) driven by the anaerobically inducible nirB promoter [25].
  • Immunisation with two doses of recombinant Salmonella expressing FH(C) from the htrA promoter gave the greatest protection, against up to 10,000 mouse lethal doses of botulinum toxin type F [26].
  • The spv and dps promoters were used to drive independent expression of the C fragment domain of tetanus toxin (TetC) from plasmids harboured in S. typhimurium SL3261 [27].

Analytical, diagnostic and therapeutic context of ccdB

  • Comparison of the parental and mutant lambda capsid proteins revealed that the relevant mutation altered the major phage head protein E. The use of toxin-free, bacteria-specific phage strains, combined with the serial-passage technique, may provide insights for developing phage into therapeutically effective antibacterial agents [4].
  • Microinjection of the catalytically active GST-SptP(C481S) protein results in changes similar to those induced by the wild-type toxin [28].
  • We believe that this is the first example of a successful oral vaccination that uses an attenuated bacterial carrier to deliver a protective antigen derived from tetanus toxin [14].
  • MAb 16E6 bound to the B subunit of SLT in Western blots and also neutralized the lethality of the toxin for mice and the enterotoxicity of the toxin in ligate rabbit ileal loops [29].
  • The enzyme-linked immunosorbent assay and the Chinese hamster ovary floating cell assay for cholera toxin have proven to be sensitive and reliable tests for determining the antigenic and biological characteristics of Salmonella toxin, respectively [30].


  1. Pathogenesis of Salmonella-mediated intestinal fluid secretion. Activation of adenylate cyclase and inhibition by indomethacin. Giannella, R.A., Gots, R.E., Charney, A.N., Greenough, W.B., Formal, S.B. Gastroenterology (1975) [Pubmed]
  2. Extracellular transport of cholera toxin B subunit using Neisseria IgA protease beta-domain: conformation-dependent outer membrane translocation. Klauser, T., Pohlner, J., Meyer, T.F. EMBO J. (1990) [Pubmed]
  3. Construction, expression, and immunogenicity of the Schistosoma mansoni P28 glutathione S-transferase as a genetic fusion to tetanus toxin fragment C in a live Aro attenuated vaccine strain of Salmonella. Khan, C.M., Villarreal-Ramos, B., Pierce, R.J., Riveau, G., Demarco de Hormaeche, R., McNeill, H., Ali, T., Fairweather, N., Chatfield, S., Capron, A. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  4. Long-circulating bacteriophage as antibacterial agents. Merril, C.R., Biswas, B., Carlton, R., Jensen, N.C., Creed, G.J., Zullo, S., Adhya, S. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  5. On the role of macrophages in anthrax. Hanna, P.C., Acosta, D., Collier, R.J. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  6. Apical secretion of a pathogen-elicited epithelial chemoattractant activity in response to surface colonization of intestinal epithelia by Salmonella typhimurium. McCormick, B.A., Parkos, C.A., Colgan, S.P., Carnes, D.K., Madara, J.L. J. Immunol. (1998) [Pubmed]
  7. Lipopolysaccharide responsiveness is an important factor in the generation of optimal antigen-specific T cell responses during infection with gram-negative bacteria. Marshall, N.E., Ziegler, H.K. J. Immunol. (1991) [Pubmed]
  8. A lethal role for lipid A in Salmonella infections. Khan, S.A., Everest, P., Servos, S., Foxwell, N., Zähringer, U., Brade, H., Rietschel, E.T., Dougan, G., Charles, I.G., Maskell, D.J. Mol. Microbiol. (1998) [Pubmed]
  9. A Salmonella typhimurium htrA live vaccine expressing multiple copies of a peptide comprising amino acids 8-23 of herpes simplex virus glycoprotein D as a genetic fusion to tetanus toxin fragment C protects mice from herpes simplex virus infection. Chabalgoity, J.A., Khan, C.M., Nash, A.A., Hormaeche, C.E. Mol. Microbiol. (1996) [Pubmed]
  10. Role of zinc in the abatement of hepatocellular damage and mortality incidence in endotoxemic rats. Sobocinski, P.Z., Powanda, M.C., Canterbury, W.J., Machotka, S.V., Walker, R.I., Snyder, S.L. Infect. Immun. (1977) [Pubmed]
  11. Toxins of molds from decaying tomato fruit. Harwig, J., Scott, P.M., Stoltz, D.R., Blanchfield, B.J. Appl. Environ. Microbiol. (1979) [Pubmed]
  12. Studies with enterotoxigenic microorganisms: effects of candidate antidiarrhoeals in experimental animals in vivo. Burke, V., Gracey, M. J. Pediatr. Gastroenterol. Nutr. (1984) [Pubmed]
  13. Distinct roles of an alternative sigma factor during both free-swimming and colonizing phases of the Vibrio cholerae pathogenic cycle. Klose, K.E., Mekalanos, J.J. Mol. Microbiol. (1998) [Pubmed]
  14. Oral vaccination of mice against tetanus by use of a live attenuated Salmonella carrier. Fairweather, N.F., Chatfield, S.N., Makoff, A.J., Strugnell, R.A., Bester, J., Maskell, D.J., Dougan, G. Infect. Immun. (1990) [Pubmed]
  15. Prior immunity to homologous and heterologous Salmonella serotypes suppresses local and systemic anti-fragment C antibody responses and protection from tetanus toxin in mice immunized with Salmonella strains expressing fragment C. Roberts, M., Bacon, A., Li, J., Chatfield, S. Infect. Immun. (1999) [Pubmed]
  16. In vitro and in vivo toxicity of T-2 toxin, a Fusarium mycotoxin, to mouse peritoneal macrophages. Vidal, D., Mavet, S. Infect. Immun. (1989) [Pubmed]
  17. Potent mutagenic activity of nitropyrenes on Chinese hamster lung cells with diphtheria toxin resistance as a selective marker. Nakayasu, M., Sakamoto, H., Wakabayashi, K., Terada, M., Sugimura, T., Rosenkranz, H.S. Carcinogenesis (1982) [Pubmed]
  18. Evidence of a role for permeability factors in the pathogenesis of salmonellosis. Peterson, J.W., Sandefur, P.D. Am. J. Clin. Nutr. (1979) [Pubmed]
  19. Specific lung mucosal and systemic immune responses after oral immunization of mice with Salmonella typhimurium aroA, Salmonella typhi Ty21a, and invasive Escherichia coli expressing recombinant pertussis toxin S1 subunit. Walker, M.J., Rohde, M., Timmis, K.N., Guzmán, C.A. Infect. Immun. (1992) [Pubmed]
  20. Salmonella enterica serovar typhimurium surA mutants are attenuated and effective live oral vaccines. Sydenham, M., Douce, G., Bowe, F., Ahmed, S., Chatfield, S., Dougan, G. Infect. Immun. (2000) [Pubmed]
  21. Refinement of a therapeutic Shiga toxin-binding probiotic for human trials. Pinyon, R.A., Paton, J.C., Paton, A.W., Botten, J.A., Morona, R. J. Infect. Dis. (2004) [Pubmed]
  22. Suicide inactivation of bacterial cystathionine gamma-synthase and methionine gamma-lyase during processing of L-propargylglycine. Johnston, M., Jankowski, D., Marcotte, P., Tanaka, H., Esaki, N., Soda, K., Walsh, C. Biochemistry (1979) [Pubmed]
  23. Immunogenicity of a Salmonella typhimurium aroA aroD vaccine expressing a nontoxic domain of Clostridium difficile toxin A. Ward, S.J., Douce, G., Figueiredo, D., Dougan, G., Wren, B.W. Infect. Immun. (1999) [Pubmed]
  24. A single dose of recombinant Salmonella typhimurium induces specific humoral immune responses against heterologous Eimeria tenella antigens in chicken. Pogonka, T., Klotz, C., Kovács, F., Lucius, R. Int. J. Parasitol. (2003) [Pubmed]
  25. Influence of preimmunization with tetanus toxoid on immune responses to tetanus toxin fragment C-guest antigen fusions in a Salmonella vaccine carrier. Chabalgoity, J.A., Villareal-Ramos, B., Khan, C.M., Chatfield, S.N., de Hormaeche, R.D., Hormaeche, C.E. Infect. Immun. (1995) [Pubmed]
  26. Vaccination against type F botulinum toxin using attenuated Salmonella enterica var Typhimurium strains expressing the BoNT/F H(C) fragment. Foynes, S., Holley, J.L., Garmory, H.S., Titball, R.W., Fairweather, N.F. Vaccine (2003) [Pubmed]
  27. Use of the stationary phase inducible promoters, spv and dps, to drive heterologous antigen expression in Salmonella vaccine strains. Marshall, D.G., Haque, A., Fowler, R., Del Guidice, G., Dorman, C.J., Dougan, G., Bowe, F. Vaccine (2000) [Pubmed]
  28. The Salmonella typhimurium tyrosine phosphatase SptP is translocated into host cells and disrupts the actin cytoskeleton. Fu, Y., Galán, J.E. Mol. Microbiol. (1998) [Pubmed]
  29. Characterization of monoclonal antibodies against Shiga-like toxin from Escherichia coli. Strockbine, N.A., Marques, L.R., Holmes, R.K., O'Brien, A.D. Infect. Immun. (1985) [Pubmed]
  30. Characterization of Salmonella toxin released by mitomycin C-treated cells. Houston, C.W., Koo, F.C., Peterson, J.W. Infect. Immun. (1981) [Pubmed]
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