Enterotoxic Clostridia: Clostridium perfringens Type A and Clostridium difficile

Bruce A. McClane; David M. Lyerly; Tracy D. Wilkins

doi:10.1128/9781555816513.ch57

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

Authors: Bruce A. McClane, David M. Lyerly, Tracy D. Wilkins

Content Type: Reference

Publication Year: 2006

Category: Bacterial Pathogenesis

Book DOI: 10.1128/9781555816513

Chapter DOI: 10.1128/9781555816513.ch57

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

Preview this chapter:

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

< Previous page | Next page > /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, Clostridium difficile and enterotoxin-positive type A strains of C. perfringens. The major lethal toxins (LTs) are not the only biomedically important C. perfringens toxins; some C. perfringens isolates, mostly belonging to type A, express C. perfringens enterotoxin (CPE). Recognized outbreaks of C. perfringens type A food poisoning are usually very large, averaging about 100 cases. C. perfringens type A food poisoning is acquired by ingestion of a food item containing vegetative cells of a CPE-positive C. perfringens type A strain. C. perfringens isolates associated with non-food-borne human gastrointestinal (GI) disease consistently carry a plasmid-borne cpe gene, which distinguishes them from food poisoning isolates carrying a chromosomal cpe gene. C. difficile is an opportunistic pathogen that causes nosocomial diarrhea and colitis after the normal GI flora has been altered, most typically by antibiotics. C. difficile-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 C. difficile 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

Full text loading...

Figures

Enterotoxic Clostridia: Clostridium perfringens Type A and Clostridium difficile

[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555816513.chap57-1,webId=/content/author/10.1128/9781555816513.chap57-1,properties={foaf_givenname=Bruce A., foaf_name=Bruce A. McClane, foaf_surname=McClane}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555816513.chap57-2,webId=/content/author/10.1128/9781555816513.chap57-2,properties={foaf_givenname=David M., foaf_name=David M. Lyerly, foaf_surname=Lyerly}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555816513.chap57-3,webId=/content/author/10.1128/9781555816513.chap57-3,properties={foaf_givenname=Tracy D., foaf_name=Tracy D. Wilkins, foaf_surname=Wilkins}]]

/content/10.1128/9781555816513.chap57.fig57-1

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 Ca2+ influx. With high CPE doses, massive Ca2+ influx occurs that triggers oncosis; with low CPE doses, there is a more moderate Ca2+ 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.

10.1128/9781555816513/fig57-1_thmb.gif

10.1128/9781555816513/fig57-1.gif

FIGURE 1

/content/10.1128/9781555816513.chap57.fig57-2

FIGURE 2

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

10.1128/9781555816513/fig57-2_thmb.gif

10.1128/9781555816513/fig57-2.gif

FIGURE 2

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

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

Enterotoxic Clostridia: Clostridium perfringens Type A and Clostridium difficile

/content/10.1128/9781555816513.chap57.tab57-1

TABLE 1

Toxin typing of C. perfringens

10.1128/9781555816513/tab57-1_thmb.gif

10.1128/9781555816513/tab57-1.gif

TABLE 1

Toxin typing of C. perfringens