Bacteriology and Pathology of Neurotoxigenic Clostridia

  • Charles L. Hatheway


Neurotoxigenic clostridia are classified in Bergey’s Manual6 as either Clostridium tetani or Clostridium botulinum. The nomenclature has been strictly determined by the kind of neurotoxin that the organisms produce. For C. tetani, the system has been satisfactory because thus far, only one phenotype of organism has been observed to produce the tetanus neurotoxin. It also remains simple in that only one serologic type of tetanus toxin has been identified. With this simplicity, it is possible to refer to organisms which have all of the same characteristics, but lack the ability to produce the neurotoxin, as nontoxigenic C. tetani. The system for naming organisms that produce botulinum neurotoxin, however, is laden with a number of problems because of the multiplicity of phenotypes and genotypes of organisms that must be included.


Toxin Gene Botulinum Neurotoxin Tetanus Toxin Clostridium Botulinum Intestinal Colonization 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Adams EB, Lawrence DR, Smith JWG. Tetanus. Blackwell Scientific Publications, 1969.Google Scholar
  2. 2.
    Aureli P, Fenicia L, Pasolini B, Gianfranceschi M, McCroskey LM, Hatheway CL. Two cases of type E infant botulism caused by neurotoxigenic Clostridium butyricum in Italy. J Infect Dis 1986; 154: 201.CrossRefGoogle Scholar
  3. 3.
    Bauer JH, Meyer KF. Human intestinal carriers of tetanus spores in California. J Infect Dis 1926; 38: 295.CrossRefGoogle Scholar
  4. 4.
    Berger SA, Cherubin CE, Nelson S, Levine L. Tetanus despite pre-existing antitetanus antibody. J Am Med Assoc 1978; 240: 769.CrossRefGoogle Scholar
  5. 5.
    Bytchenko B. Microbiology of tetanus. In: Veronesi R, ed. Tetanus: Important New Concepts. Amsterdam: Excerpta Medica, 1981.Google Scholar
  6. 6.
    Cato EP, George WL, Finegold SM. Genus Clostridium. In: Sneath PHA, Mair NS, Sharpe ME, Holt JG, eds. Bergey’s Manual of Systematic Bacteriology. Baltimore: Williams and Wilkins, 1986.Google Scholar
  7. 7.
    Chia JK, Clark JB, Ryan CA, Pollack M. Botulism in an adult associated with food-borne intestinal infection with Clostridium botulinum. N Engl J Med 1986; 315: 239.PubMedCrossRefGoogle Scholar
  8. 8.
    Davis JB, Mattman LH, Wiley M. Clostridium botulinum in a fatal wound infection. J Am Med Assoc 1951; 146: 646.PubMedCrossRefGoogle Scholar
  9. 9.
    Eisel U, Jarausch W, Goretski K, Henschen A, Engels J, Weller U, Hudel M, Habermann E, Niemann H. Tetanus toxin: primary structure, expression in E. coli and homology with botulinum toxins. EMBO J 1986; 5: 2495.Google Scholar
  10. 10.
    Eklund MW, Poysky F, Oguma K, lida H, Inoue K. Relationship of bacteriophages to toxin and hemagglutinin production and its significance in avian botulism outbreaks. In: Eklund, MW, Dowell VR Jr, eds. Avian Botulism. Springfield, IL: Charles C. Thomas, 1987.Google Scholar
  11. 11.
    Eklund MW, Poysky FT, Habig WIT. Bacteriophages and plasmids in Clostridium botulinum and Clostridium tetani and their relationship to production of toxins. In: Simpson LL, ed. Botulinum Neurotoxin and Tetanus Toxin. San Diego: Academic Press, Inc., 1989.Google Scholar
  12. 12.
    Fairweather NF, Lyness VA. The complete nucleotide sequence of tetanus toxin. Nucleic Acids Res 1986; 14: 7809.PubMedCrossRefGoogle Scholar
  13. 13.
    Finn CW, Silver RP, Habig WH, Hardegree MC, Zon G, Garon CF. The structural gene for tetanus neurotoxin is on a plasmid. Science 1984; 224: 881.PubMedCrossRefGoogle Scholar
  14. 14.
    Fujii N, Kimura K, Murakami T, Indoh T, Yashiki T, Tsuzuki K, Yokosawa N, Oguma K. The nucleotide and deduced amino acid sequences of EcoRI fragment containing the 5’-terminal region of Clostridium botulinum type E toxin gene cloned from Mashike, Iwanai and Otani strains. Microbiol Immunol 1990; 34: 1041.Google Scholar
  15. 15.
    Fujii N, Kimura K, Yashiki T, Indoh T, Murakami T, Tsuzuki K, Yokosawa N, Oguma K. Cloning of a DNA fragment encoding the 5’-terminus of the botulinum type E toxin gene from Clostridium butyricum strain BL6340. J Gen Microbiol 1991; 137: 519.PubMedCrossRefGoogle Scholar
  16. 16.
    Giménez DF, Ciccarelli AS. Another type of Clostridium botulinum. Zbl Bakt I, Abt Orig A 1970; 215: 221.Google Scholar
  17. 17.
    Giménez JA, Giménez MA, DasGupta BR. Characterization of the neurotoxin isolated from a Clostridium baratii strain implicated in infant botulism. Infect Immun 1992; 60: 518.PubMedGoogle Scholar
  18. 18.
    Giménez JA, Sugiyama, H. Comparison of toxins of Clostridium butyricum and Clostridium botulinum type E. Infect Immun 1988; 56: 926.Google Scholar
  19. 19.
    Green J, Spear H, Brinson RR. Human botulism (type F)-a rare type. Am J Med 1983; 75: 893.PubMedCrossRefGoogle Scholar
  20. 20.
    Hall JD, McCroskey LM, Pincomb BJ, Hatheway CL. Isolation of an organism resembling Clostridium barati which produces type F botulinal toxin from an infant with botulism. J Clin Microbiol 1985; 21: 654.PubMedGoogle Scholar
  21. 21.
    Hatheway CL. Botulism. In: Balows A, Hausler WH Jr, Ohashi J, Turano A, eds. Laboratory Diagnosis of Infectious Diseases. New York: Springer-Verlag, 1988.Google Scholar
  22. 22.
    Hatheway CL, McCroskey LM. Examination of feces and serum for diagnosis of infant botulism in 336 patients. J Clin Microbiol 1987; 25: 2334.Google Scholar
  23. 23.
    Hazen EL. A strain of B. botulinus not classified as type A, B, or C. J Infect Dis 1937; 60: 260.CrossRefGoogle Scholar
  24. 24.
    Laird WJ, Aaronson W, Silver RP, Habig WH, Hardegree, MC. Plasmid-associated toxigenicity in Clostridium tetani. J Infect Dis 1980; 142: 623.PubMedCrossRefGoogle Scholar
  25. 25.
    Lee WH, Rieman H. Correlation of toxic and nontoxic strains of Clostridium botulinum by DNA composition and homology. J Gen Microbiol 1970; 60: 117.PubMedCrossRefGoogle Scholar
  26. 26.
    Lee WH, Rieman, H. The genetic relatedness of proteolytic Clostridium botulinum strains. J Gen Microbiol 1970; 64: 85.PubMedCrossRefGoogle Scholar
  27. 27.
    Matsuda M. The structure of tetanus toxin. In: Simpson LL, ed. Botulinum Neurotoxin and Tetanus Toxin. San Diego: Academic Press, Inc., 1989.Google Scholar
  28. 28.
    McCroskey LM, Hatheway CL. Laboratory findings in four cases of adult botulism suggest colonization of the intestinal tract. J Clin Microbiol 1988; 26: 1052.PubMedGoogle Scholar
  29. 29.
    McCroskey LM, Hatheway CL, Fenicia L, Pasolini B, Aureli P. Characterization of an organism that produces type E botulinal toxin but which resembles Clostridium butyricum from the feces of an infant with type E botulism. J Clin Microbiol 1986; 23: 201.Google Scholar
  30. 30.
    McCroskey LM, Hatheway CL, Woodruff BA, Greenberg JA, Jurgenson P. Type F botulism due to neurotoxigenic Clostridium baratii from an unknown source in an adult. J Clin Microbiol 1991; 29: 2618.Google Scholar
  31. 31.
    Midura TF, Anion SS. Infant botulism: identification of Clostridium botulinum and its toxin in faeces. Lancet 1976; ií:934.Google Scholar
  32. 32.
    Midura TF, Nygaard GS, Wood RM, Bodily HL. Clostridium botulinum type F: isolation from venison jerky. Appl Microbiol 1972; 24: 165.PubMedGoogle Scholar
  33. 33.
    Mitamura H, Kameyama K, Ando Y. Experimental toxicoinfection in infant mice challenged with spores of Clostridium botulinum type E. Jpn J Med Sci Biol 1982; 35: 239.Google Scholar
  34. 34.
    Moller V, Scheibel I. Preliminary report on the isolation of an apparently new type of Cl. botulinum. Acta Pathol Microbiol Scand 1960; 48: 80.PubMedCrossRefGoogle Scholar
  35. 35.
    Nakamura S, Kimura I, Yamakawa K, Nishida S. Taxonomic relationships among Clostridium novyi types A and B, Clostridium haemolyticum and Clostridium botulinum type C. J Gen Microbiol 1983; 129: 1473.PubMedGoogle Scholar
  36. 36.
    Nakamura S, Okado I, Abe T, Nishida S. Taxonomy of Clostridium tetani and related species. J Gen Microbiol 1979; 113: 29.PubMedCrossRefGoogle Scholar
  37. 37.
    Nakamura S, Okado I, Nakashio S, Nishida S. Clostridium sporogenes isolates and their relationship to C. botulinum based on deoxyribonucleic acid reassociation. J Gen Microbiol 1977; 100: 395.PubMedCrossRefGoogle Scholar
  38. 38.
    Oguma K, Yokota K, Hayashi S, Takeshi K, Kumagai M, Itoh N, Tachi N, Chiba S. Infant botulism due to Clostridium botulinum type C toxin. Lancet 1990; 336: 1449.PubMedCrossRefGoogle Scholar
  39. 39.
    Passen EL, Andersen BR. Clinical tetanus despite a “protective” level of toxin-neutralizing antibody. J Am Med Assoc 1986; 255: 1171.CrossRefGoogle Scholar
  40. 40.
    Pickett J, Berg B, Chaplin E, Brunstetter MA. Syndrome of botulism in infancy: clinical and electrophysiologic study. N Engl J Med 1976; 295: 770.PubMedCrossRefGoogle Scholar
  41. 41.
    Sebald, M, Saimot G. Toxémie botulique: interét de sa mise en évidence dans le diagnostic du botulisme humain de type B. Ann Microbiol (Inst Pasteur) 1973; 124A: 61.Google Scholar
  42. 42.
    Smith LDS, Sugiyama H. Botulism: The Organism, its Toxins, the Disease. Springfield, IL: Charles C. Thomas, 1988.Google Scholar
  43. 43.
    Smith LDS, Williams BL. The Pathogenic Anaerobic Bacteria. Springfield, IL: Charles C. Thomas, 1984.Google Scholar
  44. 44.
    Sonnabend O, Sonnabend W, Heinzle R, Sigrist T, Dimhofer R, Krech U. Isolation of Clostridium botulinum type G and identification of type G botulinal toxin in humans: report of five sudden unexpected deaths. J Infect Dis 1981; 143: 22.PubMedCrossRefGoogle Scholar
  45. 45.
    Sonnabend OA, Sonnabend WF, Krech U, Molz G, Sigrist T. Continuous microbiological study of 70 sudden and unexpected infant deaths: toxigenic intestinal Clostridium botulinum infection in 9 cases of sudden infant death syndrome. Lancet 1985; ii:237.Google Scholar
  46. 46.
    Suen JC, Hatheway CL, Steigerwalt AG, Brenner DJ. Clostridium argentinense, sp. nov: a genetically homogenous group composed of all strains of Clostridium botulinum toxin type G and some nontoxigenic strains previously identified as Clostridium subterminale or Clostridium hastiforme. Int J Syst Bacteriol 1988; 38: 375.CrossRefGoogle Scholar
  47. 47.
    Suen, JC, Hatheway CL, Steigerwalt AG, Brenner DJ. Genetic confirmation of identities of neurotoxigenic Clostridium baratii and Clostridium butyricum implicated as agents of infant botulism. J Clin Microbiol 1988; 26: 2191.Google Scholar
  48. 48.
    Sugiyama H. Mouse models for infant botulism. In: Zak O, Sande MA, eds. Experimental Models in Antimicrobial Chemotherapy. New York: Academic Press, 1986.Google Scholar
  49. 49.
    Swerczek, TW. Toxicoinfectious botulism in foals and adult horses. J Am Vet Med Assoc 1980; 176: 217 (1980).Google Scholar
  50. 50.
    Ten Broeck C, Bauer JH. The tetanus bacillus as an intestinal saprophyte in man. J Exp Med 1922; 36: 261.CrossRefGoogle Scholar
  51. 51.
    Tulloch, WJ. Report of bacteriological investigations of tetanus on behalf of the war office. J Hyg 1919–20; 18: 103.Google Scholar
  52. 52.
    Van Ermengem E. Ueber einen neuen anaeroben Bacillus and seine Beziehungen zum Botulismus. Ztschr Hyg Infektionskh 1897; 26: 1.Google Scholar
  53. 53.
    Veronesi R, Bizzini B, Focaccia R, Coscina AL, Mazza CC, Focaccia T, Carraro F, Honningman MN. Naturally acquired antibodies to tetanus toxin in humans and animals from the Galapagos Islands. J Infect Dis 1983; 147: 308.PubMedCrossRefGoogle Scholar
  54. 54.
    Wells CL, Balish E. Clostridium tetani growth and toxin production in the intestines of germfree rats. Infect Immun 1983; 41: 826.PubMedGoogle Scholar
  55. 55.
    Wirz, M, Gentili G, Collotti C. Tetanus vaccine: present status. Bact Vacc 1990; 13: 35.Google Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Charles L. Hatheway
    • 1
  1. 1.Division of Bacterial and Mycotic Diseases National Center for Infectious DiseasesCenters for Disease ControlAtlantaGeorgia

Personalised recommendations