1887

Chapter 56 : Neurotoxigenic Clostridia

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in
Zoomout

Neurotoxigenic Clostridia, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816513/9781555813437_Chap56-1.gif /docserver/preview/fulltext/10.1128/9781555816513/9781555813437_Chap56-2.gif

Abstract:

This chapter describes the microbiological properties of and , with an emphasis on pathogenesis and new findings on the organisms and their clostridial neurotoxins (CNTs). Botulism is a rare but often severe paralytic disease caused by the extremely potent botulinum neurotoxins (BoNTs) produced by and certain other clostridia. The major treatment of botulism is supportive care, with careful attention being given to respiratory status. Tetanus is a vivid neurological disease characterized by violent and persistent spasms of the head, trunk, and limb muscles. Neurotoxigenic clostridia tend to grow as consortia, and pure cultures are often difficult to achieve and maintain. Owing to the complex nutrient requirements of neurotoxigenic clostridia, rich media are commonly used for cultivation. Bioassays are currently the most important laboratory tests used to identify neurotoxigenic clostridial species. Although BoNTs and tetanus neurotoxin (TeNT) are the primary determinants of virulence in neurotoxigenic clostridia, wound or intestinal infections also require additional virulence processes. The availability of genomic sequences and comparative genomic analyses, together with the development of genetic tools such as gene replacement and vectors for controlled gene expression, will be invaluable in elucidating pathogenic mechanisms of neurotoxigenic clostridia. To prevent further human illness and deaths by neurotoxic clostridia, antidotes are urgently needed that can reverse the detrimental effects of BoNTs and TeNT once they are bound and internalized in nerves.

Citation: Johnson E. 2006. Neurotoxigenic Clostridia, p 688-702. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch56

Key Concept Ranking

Human immunodeficiency virus 1
0.4765656
0.4765656
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of FIGURE 1
FIGURE 1

A boy suffering from food-borne botulism, showing the prominent effects of BoNT on the eyes and the descending paralysis to other regions of the face. (Photograph courtesy of Charles L. Hatheway [deceased], Centers for Disease Control and Prevention, Atlanta, Ga.)

Citation: Johnson E. 2006. Neurotoxigenic Clostridia, p 688-702. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch56
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2
FIGURE 2

Morphology of type A cells viewed by phase-contrast microscopy. The spore-bearing cells of other serotypes of and also have characterized morphologies, typically with swelling of the rod-shaped vegetative cell ( ).

Citation: Johnson E. 2006. Neurotoxigenic Clostridia, p 688-702. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch56
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3
FIGURE 3

Arrangement of the genes in neurotoxin gene clusters of . (Diagram courtesy of Marite Bradshaw, University of Wisconsin.)

Citation: Johnson E. 2006. Neurotoxigenic Clostridia, p 688-702. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch56
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4
FIGURE 4

Proteolytic cleavage sites and basic domain structure of BoNT/A. After proteolytic activation, the NT, consisting of an L chain and an H chain, can be defined as three basic domains: (i) L chain, catalytic domain; (ii) HN, translocation domain; and (iii) HC, receptor-binding domain. As described in the text, additional proteolytic modification takes place in BoNT/A following initial cleavage. (Diagram courtesy of Marite Bradshaw, University of Wisconsin.)

Citation: Johnson E. 2006. Neurotoxigenic Clostridia, p 688-702. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch56
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 5
FIGURE 5

Diagram of the three-dimensional structure of BoNT/A. The catalytic domain is located at the upper right, the translocation domain in the center, the N-terminal-binding subdomain at the left, and the C-terminal-binding domain at the lower left. The catalytic zinc is represented as a ball. The overall structure is 45 by 105 by 130 Å. (Image courtesy of Ray C. Stevens, University of California, Berkeley.)

Citation: Johnson E. 2006. Neurotoxigenic Clostridia, p 688-702. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch56
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555816513.chap56
1. Anttharavally, B.,, W. Tepp,, and B. R. DasGupta. 1998. Status of Cys residues in the covalent structure of botulinum neurotoxin types A, B, and E. J. Prot. Chem. 17: 187 196.
2. Arnon, S. S.,, R. Schechter,, T. V. Inglesby,, D. A. Henderson,, J. G. Bartlett,, M. Ascher,, E. Eitzen,, A. D. Fine,, J. Hauer,, M. Layton,, S. Lillibridge,, M. T. Osterholm,, E. O’Toole,, G. Parker,, T. M. Perl,, P. K. Russell,, D. L. Swerdlow,, K. Tonat, and the Working Group on Civilian Biodefense. 2001. Botulinum toxin as a biological weapon. Medical and public health management. JAMA 285: 1059 1070.
3. Arnon, S. S., 2004. Infant botulism, p. 1758-– 1766. In R. D. Feigen,, J. D. Cherry,, G. J. Demmler,, and S. L. Kaplan, (ed.), Textbook of Pediatric Infectious Diseases, 5th ed. W. B. Saunders, Philadelphia, Pa..
4. Barr, J. R.,, H. Moura,, A. E. Boyer,, A. R. Wolfitt,, S. R. Kalb,, A. Pavlopoulos,, L. G. McWilliams,, J. G. Schmidt,, R. A. Martinez,, and D. L. Ashley. 2005. Botulinum neurotoxin detection and differentiation by mass spectrometry. Emerg. Infect. Dis. 11: 1578 1583.
5. Barth, H.,, K. Aktories,, M. R. Popoff,, and B. G. Stiles. 2004. Binary bacterial toxins: biochemistry, biology, and applications of common Clostridium and Bacillus proteins. Microbiol. Mol. Biol. Rev. 68: 373 402.
6. Bleck, T. P. 1991. Tetanus: pathophysiology, management, and prophylaxis, Disease-a-Month 37: 547 603.
7. Borodic, G.,, E. Johnson,, M. Goodnough,, and E. Schantz. 1996. Botulinum toxin therapy, immunlogic resistance, and problems with available materials. Neurology 46: 26 29.
8. Bradshaw, M.,, S. S. Dineen,, N. D. Maks,, and E. A. Johnson. 2004. Regulation of neurotoxin complex expression in Clostridium botuloinum strains 62A, Hall A- hyper, and NCTC 2916. Anaerobe 10: 321 333.
9. Breidenbach, M. A.,, and A. T. Brunger. 2004. Substrate recognition for botulinum neurotoxin serotype A. Nature 432: 925 929.
10. Brüggemann, H., et al. 2003. The genome sequence of Clostridium tetani, the causative agent of tetanus disease. Proc. Natl. Acad. Sci. USA 100: 1316 1321.
11. Brüggeman, H.,, and G. Gottschalk. 2004. Insights in metabolism and toxin production from the complete genome sequence of Clostridium tetani. Anaerobe 10: 53 68.
12. Burkhard, F.,, F. Chen,, G. M. Kuziemko,, and R. C. Stevens. 1997. Electron density projection map of the botulinum neurotoxin 900-kilodalton complex by electron crystallography. J. Struct. Biol. 120: 78 84.
13. Cato, E. P.,, W. L. George,, and S. M. Finegold,. 1986. Genus Clostridium, p. 1141 1200. In P. H. A. Sneath,, N. S. Mair,, M. E. Sharpe,, and J. G. Holt (ed.), Bergey’s Manual of Systematic Bacteriology, vol. 2. The Williams & Wilkins Co., Baltimore, Md..
14. Centers for Disease Control and Prevention. 1998. Botulism in the United States, 1899-1996: Handbook for Epidemiologists, Clinicians, and Laboratory Workers. Centers for Disease Control and Prevention, Atlanta, Ga. .
15.Centers for DiseaseControl and Prevention. 1998. Media for Isolation, Characterization, and Identification of Obligately Anaerobic Bacteria. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, Atlanta, Ga..
16. Cherington, M. 1998. Clinical spectrum of botulism. Muscle Nerve 21: 701 710.
17. Collins, M. D.,, and A. K. East. 1998. Phylogeny and taxonomy of the food-borne pathogen Clostridium botulinum and its neurotoxins. J. Appl. Microbiol. 84: 5 17.
18. DasGupta, B. R., 1989. Structure of botulinum neurotoxin, p. 53 67. In L. L. Simpson (ed.), Botulinum Neurotoxin and Tetanus Toxin. Academic Press, Inc., San Diego, Calif..
19. Devriese, P. P. 1999. On the discovery of Clostridium botulinum. J. Hist. Neurosci. 8: 43 50.
20. Dineen, S. S.,, M. Bradshaw,, and E. A. Johnson. 2000. Cloning, nucleotide sequence, and expression of the gene encoding bacteriocin boticin B from Clostridium botulinum strain 213B. Appl. Environ. Microbiol. 66: 5480 5483.
21. Dineen, S. S.,, M. Bradshaw,, and E. A. Johnson. 2003. Neurotoxin gene clusters in Clostridium botulinum type A strains: sequence comparison and evolutionary implications. Curr. Microbiol. 46: 345 352.
22. Dineen, S. S.,, M. Bradshaw,, C. Karasek,, and E. A. Johnson. 2004. Nucleotide sequence and transcriptional analysis of the type A2 neurotoxin gene cluster in Clostridium botulinum. FEMS Microbiol. Lett. 235: 9 16.
23. Dong, M.,, W. H. Tepp,, E. A. Johnson,, and E. R. Chapman. 2004. Using fluorescent sensors to detect botulinum neurotoxin activity in vitro and in living cells. Proc. Natl. Acad. Sci. USA 101: 14701 14706.
24. Dong, M.,, D. A. Richards,, M. C. Goodnough,, W. H. Tepp,, E. A. Johnson,, and E. R. Chapman. 2003. Synaptotagmins I and II mediate entry of botulinum neurotoxin B into cells. J. Cell Biol. 162: 1293 1303.
25. Dürre, P. (ed.). 2005. Handbook on Clostridia. CRC Press, Boca Raton, Fla. .
26. Eklund, M. W.,, and V. R. Dowell, Jr. (ed.). 1987. Avian Botulism: an International Perspective. Charles C. Thomas, Springfield, Ill..
27. Eklund, M. W.,, F. T. Poysky,, and W. H. Habig,. 1989. Bacteriophages and plasmids in Clostridium botulinum and Clostridium tetani and their relationship to production of toxins, p. 25 51. In L. L. Simpson (ed.), Botulinum Toxin and Tetanus Toxin. Academic Press, Inc., San Diego, Calif..
28. Finegold, S. M., 1998. Tetanus, p. 693 722. In L. Collier,, A. Balows,, and M. Sussman (ed.), Topley & Wilson’s Microbiology and Microbial Infections, 9th ed., vol. 3. Bacterial Infections. Arnold, London, United Kingdom.
29. Finegold, S. M.,, D. Molitoris,, Y. Song,, C. Liu,, M.-L. Vaisanen,, E. Bolte,, M. McTeague,, R. Sandler,, H. Wexler,, E. Marlowe,, M. D. Collins,, P. Lawson,, P. Summanen,, M. Baysallar,, T. Tomzynski,, E. A. Johnson,, R. Rolfe,, H. Shah,, P. Manning,, and A. Kaul. 2002. Gastrointestinal studies in late-onset autism. Clin. Infect. Dis. 35(Suppl.1): S6 S16.
30. Finegold, S. M.,, Y. Song,, and C. Liu. 2002. Taxonomy—general comments and update on taxonomy of clostridia and anaerobic cocci. Anaerobe 8: 283 285.
31. Foran, P. G.,, N. Mohammed,, G. O. Lisk,, S. Nagwaney,, G. W. Lawrence,, E. Johnson,, L. Smith,, K. R. Aoki,, and J. O. Dolly. 2003. Evaluation of the therapeutic usefulness of botulinum neurotoxin B, C1, E, and F compared with the long lasting type A—basis for distinct durations of inhibition of exocytosis in central neurons. J. Biol. Chem. 278: 1363 1371.
32. Franciosa, G.,, P. Aureli,, and R. Schechter,. 2003. Clostridium botulinum, p. 61 89. In M. D. Miliotis, and J. W. Bier (ed.), International Handbook of Foodborne Pathogens. Marcel Dekker, Inc., New York, N.Y..
33. Giménez, D. F.,, and J. A. Giménez,. 1993. Serological subtypes of botulinal neurotoxins, p. 421 431 . In B. R. Dasgupta (ed.), Botulism and Tetanus Neurotoxins: Neurotransmission and Biomedical Aspects. Plenum Press, New York, N.Y..
34. Hanson, M. I.,, and R. C. Stevens,. 2002. Structural view of botulinum neurotoxin in numerous functional states, p. 11 27. In M. F. Brin,, M. Hallett,, and J. Jankovic (ed.), Scientific and Therapeutic Aspects of Botulinum Toxin. Lippincott, Williams, and Wilkins, Philadelphia, Pa..
35. Hatheway, C. L., 1988. Botulism, p. 111 133. In A. Balows,, J. W. J. Hausler,, M. Ohashi,, and A. Turano (ed.), Laboratory Diagnosis of Infectious Diseases: Principles and Practice. Springer-Verlag, New York, N.Y..
36. Hatheway, C. L.,, and E. A. Johnson,. 1998. Clostridium: the spore-bearing anaerobes, p. 731 782. In L. Collier,, A. Balows,, and M. Sussman (ed.), Topley & Wilson’s Microbiology and Microbial Infections, 9th ed., vol. 2. Systematic Bacteriology. Arnold, London, United Kingdom.
37. Hoch, J. A.,, and M. Perego. 1999. Two-component signal transduction in Bacillus subtilis: how one organism sees its world. J. Bacteriol. 181: 1975 1983.
38. Holdeman, L. V.,, E. P. Cato,, and W. E. C. Moore. 1979. Anaerobe Laboratory Manual, 4th ed. Virginia Polytechic Institute and State University, Blacksburg, Va..
39. Humeau, Y.,, F. Doussau,, N. J. Grant,, and B. Poulain. 2000. How botulinum and tetanus neurotoxins block neurotransmitter release. Biochimie 82: 427 446.
40. Ivanova, N.,, A. Sorokin,, I. Anderson,, N. Galleron,, B. Candelon,, V. Kapatral,, A. Bhattacharya,, G. Reznik,, N. Mikhailova,, A. Lapidus,, L. Chu,, M. Mazur,, E. Goltzman,, N. Larsen,, M. D’Souza,, M. Walunas,, Y. Grechkin,, G. Pusch,, R. Haselkorn,, M. Fonstein,, S. D. Ehrlich,, R. Overbeek,, and N. Kyripides. 2003. Genome sequence of Bacillus cereus and comparative analysis with Bacillus anthracis. Nature 243: 87 91.
41. Johnson, E. A. 1999. Clostridial toxins as therapeutic agents: benefits of nature’s most toxic proteins. Annu. Rev. Microbiol. 53: 551 575.
42. Johnson, E. A., 2005. Clostridial neurotoxins, p. 491 525. In P. Dürre (ed.), Handbook on Clostridia. CRC Press, Boca Raton, Fla..
43. Johnson, E. A., 2005. Bacteriophages encoding botulinum and diphtheria toxin, p. 280 296. In M. Waldor,, D. I. Friedman,, and S. L. Adhya (ed.), Phages: Their Role in Bacterial Pathogenesis and Biotechnology. ASM Press, Washington, D.C..
44. Johnson, E. A., 2005. Clostridium botulinum and Clostridium tetani, p. 1035 1088. In S. P. Borrelio,, P. R. Murray,, and G. Funke (ed.), Topley and Wilson’s Microbiology and Microbial Infections, vol. 10. Bacteriology, vol. 2. Hodder Arnold, London, United Kingdom.
45. Johnson, E. A.,, and M. Bradshaw. 2001. Clostridium botulinum: a metabolic and cellular perspective. Toxicon 39: 1703 1722.
46. Johnson, E. A.,, and M. C. Goodnough,. 1998. Botulism, p. 723 741. In L. Collier,, A. Balows,, and M. Sussman (ed.), Topley & Wilson’s Microbiology and Microbial Infections, 9th ed., vol. 2. Systematic Bacteriology. Arnold, London, United Kingdom.
47. Keller, J. E.,, and E. A. Neale. 2001. The role of synaptic protein Sanp-25 in the potency of botulinum neurotoxin type A. J. Biol. Chem. 276: 13476 13482.
48. Koriazova, L. K.,, and M. Montal. 2003. Translocation of botulinum neurotoxin light chain protease through the heavy chain channel. Nat. Struct. Biol. 10: 13 18.
49. Kubota, T.,, N. Yonekura,, Y. Hariya,, E. Iosgai,, H. Isogai,, K. Amano,, and N. Fujii. 1998. Gene arrangement in the upstream region of Clostridium botulinum type E and Clostridium butyricum BL6340 is different from that of other types. FEMS Microbiol. Lett. 158: 215 221.
50. Lacy, D. B.,, and R. C. Stevens. 1999. Sequence homology and structural analysis of the clostridial neurotoxins, J. Mol. Biol. 291: 1091 1104.
51. Lacy, D. B.,, W. Tepp,, A. C. Cohen,, B. R. DasGupta,, and R. C. Stevens. 1998. Crystal structure of botulinum neurotoxin type A and implications for toxicity. Nat. Struct. Biol. 5: 898 902.
52. Lalli, G.,, S. Bohnert,, K. Deinhardt,, C. Verastegui,, and G. Schiavo. 2003. The journey of tetanus and botulinum neurotoxins in neurons. Trends Microbiol. 11: 431 437.
53. Malizio, C. J.,, M. C. Goodnough,, and E. A. Johnson. 2000. Purification of botulinum type A neurotoxin. Methods Mol. Biol. 145: 27 39.
54. Miyamoto, O.,, J. Minami,, T. Toyoshima,, T. Nakamura,, T. Masada,, S. Nagao,, T. Negi,, T. Itano,, and A. Okabe. 1998. Neurotoxicity of Clostridium perfringens epsilon-toxin for the rat hippocampus via the glutamatergic system. Infect. Immun. 66: 2501 2508.
55. Montecucco, C.,, and G. Schiavo. 1995. Structure and function of tetanus and botulinum neurotoxins. Q. Rev. Biophys. 28: 423 472.
56. Moorthy, J.,, G. A. Mensing,, D. Kim,, S. Mohanty,, D. T. Eddington,, W. H. Tepp,, E. A. Johnson,, and D. J. Beebe. 2004. Microfluidic tectonics platform: a colorimetric, disposable botulinum toxin enzyme-linked immunosorbent assay system. Electrophoresis 25: 1705 1713.
57. Nölling, J.,, G. Breton,, M. V. Omelchenko,, K. S. Makarova,, Q. Zeng,, R. Gibson,, H. M. Lee,, J. Dubois,, D. Qiu,, J. Hitti,, Y. I. Wolf,, R. L. Tatusov,, F. Sabathe,, L. Doucette-Stamm,, P. Soucaille,, M. J. Daly,, G. N. Bennett,, E. V. Koonin,, and D. R. Smith. 2001. Genome sequence and comparative analysis of the solvent-producing bacterium Clostridium acetobutylicum. J. Bacteriol. 183: 4823 4828.
58. Porfirio, Z.,, S. M. Prado,, M. D. C. Vancetto,, F. Fratelli,, E. W. Alves,, I. Raw,, B. L. Fernandes,, A. C. M. Camargo,, and I. Lebrun. 1997. Specific peptides of casein pancreatic digestion enhance the production of tetanus toxin. J. Appl. Microbiol. 83: 678 684.
59. Quinn, C. P.,, and N. P. Minton,. 2001. Clostridial neurotoxins, p. 211 250 In H. Bahl, and R. Dürre (ed.), Clostridia: Biotechnology and Medical Applications. Wiley-VCH, Weinheim, Germany.
60. Raffestin, S.,, J. Christophe Marvaud,, R. Cerrato,, B. Dupuy,, and M. R. Popoff. 2004. Organization and regulation of the neurotoxin genes in Clostridium botulinum and Clostridium tetani. Anaerobe 10: 93 100.
61. Ratts, R.,, H. Zeng,, E. A. Berg,, M. E. McComb,, C. E. Costello,, J. C. vanderSpek,, and J. R. Murphy. 2003. The cytosolic entry of diphtheria toxin catalytic domain requires a host cell cytosolic translocation complex. J. Cell Biol. 160: 1139 1150.
62. Read, T. D.,, S. N. Peterson,, N. Tourasse,, L. W. Baille, et al. 2003. The genome sequence of Bacillus anthracis and its comparison to closely related bacteria. Nature 423: 81 86.
63. Sakaguchi, G. 1983. Clostridium botulinum toxins. Pharmacol. Ther. 19: 165 194.
64. Schantz, E. J.,, and E. A. Johnson. 1992. Properties and use of botulinum toxin and other microbial neurotoxins in medicine. Microbiol. Rev. 56: 80 99.
65. Schiavo, G.,, M. Matteoli,, and C. Montecucco. 2000. Neurotoxins affecting neuroexocytosis. Physiol. Rev. 80: 717 766.
66. Shimizu, T.,, K. Ohtani,, H. Hirakawa,, K. Ohshima,, A. Yamashita,, T. Shiba,, N. Ogasawara,, M. Hattori,, S. Kuhara,, and H. Hayashi. 2002. Complete genome sequence of Clostridium perfringens, an anaerobic flesh-eater. Proc. Natl. Acad. Sci. USA 99: 996 2001.
67. Simpson, L. L. 2004. Identification of the major steps in botulinum toxin action. Annu. Rev. Pharmacol. Toxicol. 44: 167 193.
68. Smith, L. D. S.,, and H. Sugiyama. 1988. Botulism: the Organism, Its Toxins, the Disease. Charles C Thomas, Springfield, Ill..
69. Solomon, H. M.,, E. A. Johnson,, D. T. Bernard,, S. S. Arnon,, and J. L. Ferreira,. 2001. Clostridium botulinum and its toxins, p. 317 324. In F. P. Downes, and K. Ito (ed.), Compendium for the Microbiological Examination of Foods, 4th ed. American Public Health Association, Washington, D.C..
70. Sugiyama, H. 1980. Clostridium botulinum neurotoxin. Microbiol. Rev. 44: 419 448.
71. Swaminathan, S.,, S. Eswaramoorthy,, and D. Kumaran. 2004. Structure and activity of botulinum neurotoxins. Mov. Disord. 19(Suppl. 8): S17 S22.
72. Turton, K.,, J. A. Chaddock,, and K. R. Acharya. 2002. Botulinum and tetanus neurotoxins: structure, function, and therapeutic utility. Trends Biochem. Sci. 27: 552 558.
73. Van Ermengem, E. 1979. Classics in infectious disease. A new anaerobic bacillus and its relation to botulism. Rev. Infect. Dis. 1:701-719. [Reprint, Z. Hyg. Infektionskr. 26: 1 56, 1897.]
74. Willis, A. T. 1969. Clostridia of Wound Infection. Butterworths, London, United Kingdom.

Tables

Generic image for table
TABLE 1

Properties of botulinum (BoNT) and tetanus (TeNT) neurotoxins

Gene location: C, chromosome; B, bacteriophage; P, plasmid. For putative chromosomal locations, this location is inferred from PCR amplification of chromosomal DNA preparations, except for type A, in which toxin gene mutations have been mapped to the chromosome (see references and ).

Specific toxicity refers to toxins activated by trypsinization when necessary for maximum toxicity. Toxicities are per milligram of protein. Most of the reported data are from Sugiyama ( ). The toxicities can vary considerably depending upon the strain, growth conditions, and other factors, and these specific activities are only representative of experiments conducted by Sugiyama ( ). Studies ( ) have shown that oral doses of type A or B toxin complexes in mice are 10 to 1,000 times greater than the intraperitoneal or intravenous lethal dose depending on the size of the complex, diluent, and other factors.

The specific peptide bond cleaved is shown. However, the clostridial neurotoxins require a minimum peptide length of >14 amino acid residues, depending on the serotype and a characteristic substrate tertiary structure for catalytic activity.

Citation: Johnson E. 2006. Neurotoxigenic Clostridia, p 688-702. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch56

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error