1887

Chapter 57 : Enterotoxic Clostridia: Clostridium perfringens Type A and Clostridium difficile

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

Preview this chapter:
Zoom in
Zoomout

Enterotoxic Clostridia: Clostridium perfringens Type A and Clostridium difficile, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816513/9781555813437_Chap57-1.gif /docserver/preview/fulltext/10.1128/9781555816513/9781555813437_Chap57-2.gif

Abstract:

This chapter discusses two enterotoxin-producing clostridia that rank among the most important enteric pathogens of humans, and enterotoxin-positive type A strains of . The major lethal toxins (LTs) are not the only biomedically important toxins; some isolates, mostly belonging to type A, express enterotoxin (CPE). Recognized outbreaks of type A food poisoning are usually very large, averaging about 100 cases. type A food poisoning is acquired by ingestion of a food item containing vegetative cells of a CPE-positive type A strain. isolates associated with non-food-borne human gastrointestinal (GI) disease consistently carry a plasmid-borne gene, which distinguishes them from food poisoning isolates carrying a chromosomal gene. is an opportunistic pathogen that causes nosocomial diarrhea and colitis after the normal GI flora has been altered, most typically by antibiotics. -mediated disease develops from the production of two toxins, toxin A and toxin B, which in some papers are referred to as the enterotoxin and cytotoxin, respectively. Toxin production occurs during the stationary phase, under conditions that limit the growth of the organism. Certain basic precautions should be taken to help control outbreaks of disease. In most instances, the incidence of disease can be reduced simply by educating health care workers about the disease and how it is spread.

Citation: McClane B, Lyerly D, Wilkins T. 2006. Enterotoxic Clostridia: Clostridium perfringens Type A and Clostridium difficile, p 703-714. 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.ch57

Key Concept Ranking

Clostridium perfringens Type A
0.47427493
0.47427493
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of FIGURE 1
FIGURE 1

Model for the mechanism of action of CPE. (A) CPE binds to receptors, forming a small complex. At 37°C, the small complex interacts with other proteins to form an ∼155-kDa large complex. The ∼155-kDa complex is a pore that allows Ca influx. With high CPE doses, massive Ca influx occurs that triggers oncosis; with low CPE doses, there is a more moderate Ca influx that triggers apoptosis. Activation of either cell death pathway causes morphologic damage that exposes receptors on the basolateral surface of the intoxicated cell and adjacent cells to still-unbound CPE. This allows additional formation of the ∼155-kDa large complex and also permits bound CPE to interact with occludin to form an ∼200-kDa complex. Formation of those two large CPE complexes triggers internalization of tight junction proteins, which damages the tight junction and leads to paracellular permeability alterations that contribute to CPE-induced diarrhea.

Citation: McClane B, Lyerly D, Wilkins T. 2006. Enterotoxic Clostridia: Clostridium perfringens Type A and Clostridium difficile, p 703-714. 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.ch57
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2
FIGURE 2

(A) PaLoc carrying the and genes of . The DNA region comprising the PaLoc is approximately 19.6 kb. (B) Structural features conserved between toxins A and B.

Citation: McClane B, Lyerly D, Wilkins T. 2006. Enterotoxic Clostridia: Clostridium perfringens Type A and Clostridium difficile, p 703-714. 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.ch57
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555816513.chap57
1. Aktories, K.,, and I. Just. 1995. Monoglucosylation of low-molecular-mass GTP-binding Rho proteins by clostridial cytotoxins. Trends Cell Biol. 5: 441 443.
2. Barroso, L. A.,, J. S. Moncrief,, D. M. Lyerly,, and T. D. Wilkins. 1994. Mutagenesis of the Clostridium difficile toxin B genes and effect on cytotoxic activity. Microb. Pathog. 16: 297 303.
3. Bartlett, J. G. 1994. Clostridium difficile: history of its role as an enteric pathogen and the current state of knowledge about the organism. Clin. Infect. Dis. 18: S265 S272.
4. Bartlett, J. G., 1995. Antibiotic-associated diarrhea, p. 893 904. In M. J. Blaser,, P. D. Smith,, J. I. Ravdin,, H. B. Greenberg,, and R. L. Guerrant (ed.), Infections of the Gastrointestinal Tract. Raven Press, New York, N.Y.
5. Billington, S. J.,, E. U. Wieckowski,, M. R. Sarker,, D. Bueschel,, J. G. Songer,, and B. A. McClane. 1998. Clostridium perfringens type E animal isolates with highly conserved, silent enterotoxin gene sequences. Infect. Immun. 66: 4531 4536.
6. Bongaerts, G. P. A.,, and D. M. Lyerly. 1997. Role of bacterial metabolism and physiology in the pathogenesis of Clostridium difficile disease. Microb. Pathog. 22: 253 256.
7. Borriello, S. P. 1990. Pathogenesis of Clostridium difficile of the gut. J. Med. Microbiol. 33: 207 215.
8. Borriello, S. P.,, H. A. Davies,, and F. E. Barclay. 1988. Detection of fimbriae amongst strains of Clostridium difficile. FEMS Microbiol. Lett. 49: 65 67.
9. Borriello, S. P.,, H. E. Lawson,, F. E. Barclay,, and A. R. Welch,. 1987. Clostridium perfringens enterotoxin-associated diarrhoea, p. 33 42. In S. P. Borriello (ed.), Recent Advances in Anaerobic Microbiology. Martinus Nijhoff, Boston, Mass.
10. Braun, M.,, C. Herholz,, R. Straub,, B. Choisat,, J. Frey,, J. Nicolet,, and P. Kuhnert. 2000. Detection of the ADP-ribosyltransferase toxin gene ( cdtA) and its activity in Clostridium difficile isolates from Equidae. FEMS Microbiol. Lett. 184: 29 33.
11. Braun, V.,, T. Hundsberger,, P. Leukel,, M. Sauerborn,, and C. von Eichel-Streiber. 1996. Definition of the single integration site of the pathogenicity locus in Clostridium difficile. Gene 181: 29 38.
12. Brazier, J. S. 1998. The diagnosis of Clostridium difficile-associated disease. J. Antimicrob. Chemother. 41: 29 40.
13. Brynestad, S.,, and P. E. Granum. 1999. Evidence that Tn 5565, which includes the enterotoxin gene in Clostridium perfringens, can have a circular form which may be a transposition intermediate. FEMS Microbiol. Lett. 170: 281 286.
14. Brynestad, S.,, M. R. Sarker,, B. A. McClane,, P. E. Granum,, and J. I. Rood. 2001. Conjugative transfer of the plasmid carrying the Clostridium perfringens enterotoxin gene. Infect. Immun. 69: 3483 3487.
15. Carman, R. J. 1997. Clostridium perfringens in spontaneous and antibiotic-associated diarrhoea of man and other animals. Rev. Med. Microbiol. 8( Suppl. 1): S43 S46.
16. Chakrabarti, G.,, and B. A. McClane. 2005. The importance of calcium influx, calpain, and calmodulin for the activation of CaCo-2 cell death pathways by Clostridium perfringens enterotoxin. Cell. Microbiol. 7: 129 146.
17. Chakrabarti, G.,, X. Zhou,, and B. A. McClane. 2003. Death pathways activated in CaCo-2 cells by Clostridium perfringens enterotoxin. Infect. Immun. 71: 4260 4270.
18. Collie, R. E.,, J. F. Kokai-Kun,, and B. A. McClane. 1998. Phenotypic characterization of enterotoxigenic Clostridium perfringens isolates from non-foodborne human gastrointestinal diseases. Anaerobe 4: 69 79.
19. Collie, R. E.,, and B. A. McClane. 1998. Evidence that the enterotoxin gene can be episomal in Clostridium perfringens isolates associated with non-food-borne human gastrointestinal diseases. J. Clin. Microbiol. 36: 30 36.
20. Cornillot, E.,, B. Saint-Joanis,, G. Daube,, S. Katayama,, P. E. Granum,, B. Carnard,, and S. T. Cole. 1995. The enterotoxin gene ( cpe) of Clostridium perfringens can be chromosomal or plasmid-borne. Mol. Microbiol. 15: 639 647.
21. Delmee, M. 1989. Clostridium difficile infection in healthcare workers. Lancet ii: 1095.
22. Dove, C. H.,, S. Z. Wang,, S. B. Price,, C. J. Phelps,, D. M. Lyerly,, T. D. Wilkins,, and J. L. Johnson. 1990. Molecular characterization of the Clostridium difficile toxin A gene. Infect. Immun. 58: 480 488.
23. Dupuy, B.,, and A. L. Sonenshein. 1998. Regulated transcription of Clostridium difficile toxin genes. Mol. Microbiol. 27: 107 120.
24. Fujita, K.,, J. Katahira,, Y. Horiguchi,, N. Sonoda,, M. Furuse,, and S. Tsukita. 2000. Clostridium perfringens enterotoxin binds to the second extracellular loop of claudin-3, a tight junction integral membrane protein. FEBS Lett. 476: 258 261.
25. George, W. L.,, V. L. Sutter,, D. Citron,, and S. M. Finegold. 1979. Selective and differential medium for isolation of Clostridium difficile. J. Clin. Microbiol. 9: 214 219.
26. Goncalves, C.,, D. Decre,, F. Barbut,, B. Burghoffer,, and J. C. Petit. 2004. Prevalence and characterization of a binary toxin (actin-specific ADP-ribosyltransferase) from Clostridium difficile. J. Clin. Microbiol. 42: 1933 1939.
27. Gulke, I.,, G. Pfeifer,, J. Liese,, M. Fritz,, F. Hofmann,, K. Aktories,, and H. Barth. 2001. Characterization of the enzymatic component of the ADP-ribosyltransferase toxin CDTa from Clostridium difficile. Infect. Immun. 69: 6004 6011.
28. Hammond, G. A.,, and J. L. Johnson. 1995. The toxigenic element of Clostridium difficile strain VPI 10463. Microb. Pathog. 19: 203 213.
29. Hardy, S. P.,, C. Ritchie,, M. C. Allen,, R. H. Ashley,, and P. E. Granum. 2001. Clostridium perfringens type A enterotoxin forms mepacrine-sensitive pores in pure phospholipid bilayers in the absence of putative receptor proteins. Biochim. Biophys. Acta 1515: 38 43.
30. Hofmann, F.,, C. Busch,, U. Prepens,, I. Just,, and K. Aktories. 1997. Localization of the glucosyltransferase activity of Clostridium difficile toxin B to the N-terminal part of the holotoxin. J. Biol. Chem. 272: 11074 11078.
31. Huang, I. H.,, M. Waters,, R. R. Grau,, and M. R. Sarker. 2004. Disruption of the gene (spoOA) encoding sporulation transcription factor blocks endospore formation and enterotoxin production in enterotoxigenic Clostridium perfringens type A. FEMS Microbiol. Lett. 233: 233 240.
32. Johnson, J. L.,, C. Phelps,, L. Barroso,, M. D. Roberts,, D. M. Lyerly,, and T. D. Wilkins. 1990. Cloning and expression of the toxin B gene of Clostridium difficile. Curr. Microbiol. 20: 397 401.
33. Johnson, S.,, W. D. Sypura,, D. N. Gerding,, S. L. Ewing,, and E. N. Janoff. 1995. Selective neutralization of a bacterial enterotoxin by serum immunoglobulin A in response to mucosal disease. Infect. Immun. 63: 3166 3173.
34. Katahira, J.,, N. Inoue,, Y. Horiguchi,, M. Matsuda,, and N. Sugimoto. 1997. Molecular cloning and functional characterization of the receptor for Clostridium perfringens enterotoxin. J. Cell Biol. 136: 1239 1247.
35. Katahira, J.,, H. Sugiyama,, N. Inoue,, Y. Horiguchi,, M. Matsuda,, and N. Sugimoto. 1997. Clostridium perfringens enterotoxin utilizes two structurally related membrane proteins as functional receptors in vivo. J. Biol. Chem. 272: 26652 26658.
36. Kim, P. H.,, J. P. Iaconis,, and R. D. Rolfe. 1987. Immunization of adult hamsters against Clostridium difficile-associated ileocecitis and transfer of protection to infant hamsters. Infect. Immun. 55: 2984 2992.
37. Knoop, F. C.,, M. Owen,, and I. C. Crocker. 1993. Clostridium difficile: clinical disease and diagnosis. Clin. Microbiol. Rev. 6: 251 265.
38. Kokai-Kun, J. F.,, and B. A. McClane. 1996. Evidence that a region(s) of the Clostridium perfringens enterotoxin molecule remains exposed on the external surface of the mammalian plasma membrane when the toxin is sequestered in small or large complexes. Infect. Immun. 64: 1020 1025.
39. Kokai-Kun, J. F.,, and B. A. McClane. 1997. Deletion analysis of the Clostridium perfringens enterotoxin. Infect. Immun. 65: 1014 1022.
40. Libby, J. M.,, B. S. Jortner,, and T. D. Wilkins. 1982. Effects of the two toxins of Clostridium difficile in antibiotic-associated cecitis in hamsters. Infect. Immun. 36: 822 829.
41. Lyerly, D. M. 1993. Epidemiology of Clostridium difficile disease. Clin. Microbiol. Newsl. 15: 49 52.
42. Lyerly, D. M.,, L. A. Barroso,, and T. D. Wilkins. 1991. Identification of the latex-reactive protein of Clostridium difficile as glutamate dehydrogenase. J. Clin. Microbiol. 29: 2639 2642.
43. Lyerly, D. M.,, and T. D. Wilkins,. 1995. Clostridium difficile, p. 867 891. In M. J. Blaser,, P. D. Smith,, J. I. Ravdin,, H. B. Greenberg,, and R. L. Guerrant (ed.), Infections of the Gastrointestinal Tract. Raven Press, New York, N.Y.
44. Magdesian, K. G.,, J. E. Madigan,, D. C. Hirsh,, S. S. Jang,, Y. J. Tang,, T. E. Carpenter,, L. M. Hansen,, and J. Silva, Jr. 1997. Clostridium difficile and horses: a review. Rev. Med. Microbiol. 8: S46 S48.
45. Mani, N.,, D. Lyras,, L. Barroso,, P. Howarth,, T. Wilkins,, J. I. Rood,, A. L. Sonenshein,, and B. Dupuy. 2002. Environmental response and autoregulation of Clostridium difficile txeR, a sigma factor for toxin gene expression. J. Bacteriol. 184: 5971 5978.
46. McClane, B. A. 2000. Clostridium perfringens enterotoxin and intestinal tight junctions. Trends Microbiol. 8: 145 146.
47. McClane, B. A., 2000. The action, genetics and synthesis of Clostridium perfringens enterotoxin, p. 247 272. In J. W. Cary,, M. A. Stein,, and D. Bhatnagar (ed.), Microbial Food-borne Diseases: Mechanisms of Pathogenesis and Toxin Synthesis. Technomic Press, Lancaster, Pa.
48. McClane, B. A., 2001. Clostridium perfringens, p. 351 372. In M. P. Doyle,, L. R. Beuchat,, and T. J. Montville (ed.), Food Microbiology: Fundamentals and Frontiers, 2nd ed. ASM Press, Washington, D.C.
49. McFarland, L. V.,, and G. W. Elmer. 1995. Biotherapeutic agents: past, present and future. Microecol. Ther. 23: 46 73.
50. McFarland, L. V.,, C. M. Surawicz,, and W. E. Stamm. 1990. Risk factors for Clostridium difficile carriage and C. difficile-associated diarrhea in a cohort of hospitalized patients. J. Infect. Dis. 162: 678 684.
51. Miyamoto, K.,, G. Chakrabarti,, Y. Morino,, and B. A. McClane. 2002. Organization of the plasmid cpe locus of Clostridium perfringens type A isolates. Infect. Immun. 70: 4261 4272.
52. Moncrief, J. S.,, L. A. Barroso,, and T. D. Wilkins. 1997. Positive regulation of Clostridium difficile toxins. Infect. Immun. 65: 1105 1108.
53. Moncrief, J. S.,, D. M. Lyerly,, and T. D. Wilkins,. 2000. Molecular biology of large clostridial toxins, p. 333 359. In K. Aktories, and I. Just (ed.), Handbook of Experimental Pharmacology. Springer-Verlag, Berlin, Germany.
54. Onderdonk, A. B., 1988. Role of the hamster model of antibiotic-associated colitis in defining the etiology of the disease, p. 115 125. In R. D. Rolfe, and S. M. Finegold (ed.), Clostridium difficile: Its Role in Intestinal Disease. Academic Press, Inc., New York, N.Y.
55. Perelle, S.,, M. Gibert,, P. Bourlioux,, G. Corthier,, and M. R. Popoff. 1997. Production of a complete binary toxin (actin-specific ADP-ribosyltransferase) by Clostridium difficile CD196. Infect. Immun. 65: 1402 1407.
56. Pothoulakis, C.,, I. Castagliuolo,, C. P. Kelly,, and J. T. Lamont. 1993. Clostridium difficile-associated diarrhea and colitis: pathogenesis and therapy. Int. J. Antimicrob. Agents 3: 17 32.
57. Rupnik, M. 2002. Binary toxin-producing Clostridium difficile. Anaerobe 8: 164 165.
58. Rupnik, M.,, V. Avesani,, M. Janc,, C. von Eichel-Streiber,, and M. Delmee. 1998. A novel toxinotyping scheme and correlation of toxinotypes with serogroups of Clostridium difficile isolates. J. Clin. Microbiol. 36: 2240 2247.
59. Sarker, M. R.,, R. J. Carman,, and B. A. McClane. 1999. Inactivation of the gene ( cpe) encoding Clostridium perfringens enterotoxin eliminates the ability of two cpe-positive C. perfringens type A human gastrointestinal disease isolates to affect rabbit ileal loops. Mol. Microbiol. 33: 946 958.
60. Sarker, M. R.,, R. P. Shivers,, S. G. Sparks,, V. K. Juneja,, and B. A. McClane. 2000. Comparative experiments to examine the effects of heating on vegetative cells and spores of Clostridium perfringens isolates carrying plasmid versus chromosomal enterotoxin genes. Appl. Environ. Microbiol. 66: 3234 3240.
61. Shih, N. J.,, and R. G. Labbe. 1996. Sporulation-promoting ability of Clostridium perfringens culture fluids. Appl. Environ. Microbiol. 62: 1441 1443.
62. 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 1001.
63. Singh, U.,, C. M. Van Italie,, L. L. Mitic,, J. M. Anderson,, and B. A. McClane. 2000. CaCo-2 cells treated with Clostridium perfringens enterotoxin form multiple large complex species, one of which contains the tight junction protein occludin. J. Biol. Chem. 275: 18407 18417.
64. Singh, U.,, L. L. Mitic,, E. U. Wieckowski,, J. M. Anderson,, and B. A. McClane. 2001. Comparative biochemical and immunocytochemical studies reveal differences in the effects of Clostridium perfringens enterotoxin on polarized CaCo-2 cells versus Vero cells. J. Biol. Chem. 276: 33402 33412.
65. Smedley, J. G., III,, and B. A. McClane. 2004. Fine mapping of the N-terminal cytotoxicity region of Clostridium perfringens enterotoxin by site-directed mutagenesis. Infect. Immun. 72: 6914 6923.
66. Songer, J. G. 1996. Clostridial enteric diseases of domestic animals. Clin. Microbiol. Rev. 9: 216 234.
67. Torres, J. F. 1991. Purification and characterization of toxin B from a strain of Clostridium difficile that does not produce toxin A. J. Med. Microbiol. 35: 40 44.
68. Varga, J.,, V. L. Stirewalt,, and S. B. Melville. 2004. The CcpA protein is necessary for efficient sporulation and enterotoxin gene ( cpe) regulation in Clostridium perfringens. J. Bacteriol. 186: 5221 5229.
69. von Eichel-Streiber, C.,, M. Sauerborn,, and H. K. Kuramitsu. 1992. Evidence for a modular structure of the homologous repetitive C-terminal carbohydrate-binding sites of Clostridium difficile toxins and Streptococcus mutans glucosyltransferases. J. Bacteriol. 174: 6707 6710.
70. Wieckowski, E. U.,, J. F. Kokai-Kun,, and B. A. McClane. 1998. Characterization of membrane-associated Clostridium perfringens enterotoxin following pronase treatment. Infect. Immun. 66: 5897 5905.
71. Zhao, Y.,, and S. B. Melville. 1998. Identification and characterization of sporulation-dependent promoters upstream of the enterotoxin gene ( cpe) of Clostridium perfringens. J. Bacteriol. 180: 136 142.

Tables

Generic image for table
TABLE 1

Toxin typing of

Citation: McClane B, Lyerly D, Wilkins T. 2006. Enterotoxic Clostridia: Clostridium perfringens Type A and Clostridium difficile, p 703-714. 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.ch57

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