contadores
Skip to main navigation menu Skip to main content Skip to site footer
##common.pageHeaderLogo.altText##

Review Article

Vol. 38 No. 2 (2021): Revista de Ciencias Agrícolas - Second semester, July - December 2021

Pathologic findings on ruminant enteric clostridial diseases reveal specificities and differences among iota and iota-like toxins

  • Helio S Brito
  • Fernando Camargo Alencar
  • Benedito Albuquerque
  • Marcos G Silva
  • Mellanie KC Felix
  • Daniel S Mulholland
  • Eugênio E Oliveira
  • Luis André M Mariúba
  • Eliane M Sobrinho
  • Igor V Brandi
  • Francisco Carlos F Lobato
  • Alex Sander R Cangussu ▸
DOI
https://doi.org/10.22267/rcia.213802.154
Submitted
June 7, 2021
Published
2021-09-29

Abstract

The iota toxin (ITX) is a binary enterotoxin produced as a protoxin by Clostridium perfringens (C. perfringens) type E that is activated by proteolytic enzymes in the small intestine of infected animals. By depolymerization of the actin filaments, ITX causes cytoskeleton disorganization of cells promoting the increase of the cell permeability. Here, we conducted this review aiming to advance the understanding of enteric clostridial diseases caused by C. perfringens toxins and the specificity of ITX in the intestinal mucosa lesions. ITX consists of an enzymatic component (Ia) and a binding component (Ib). We screened the recently published histological findings of the ITX effects and its relationship with intestinal enteric diseases. Histologically, hemorrhagic necrosis and multifocal hemorrhage have been observed in the jejunum-ileum mucosa, the small intestine, and the abomasum. Although the diagnosis is still based on the presence of toxins in the intestinal contents and the clinical and/or histological history, it is important to develop novel enterotoxemic indicators capable of establishing precise methods for differentiate the actions of ITX and other toxins involved in the infectious process of C. perfringens type E.

References

  1. Alves, G. G.; R. A. M. de Ávila; Chávez-Olórtegui, C. D.; Lobato, F. C. F. (2014). Clostridium perfringens epsilon toxin: The third most potent bacterial toxin known. Anaerobe. 30: 102-107. doi: 10.1016/j.anaerobe.2014.08.016
  2. Assis-Rodrigues, M.; Rodrigues-Sartori, S.; Santos-Totaro, P.; Pinto da Matta, S. (2019). Hystometric evaluation of nickel chronic exposure effects on large instestine of adult Wistar male rats. Revista de Ciencias Agrícolas. 36 (E): 21-30. doi: 10.22267/rcia.1936E.103
  3. Awad, M. M.; Bryant, A. E.; Stevens, D. L.; Rood, J. I. (1995). Virulence studies on chromosomal α‐toxin and Θ‐toxin mutants constructed by allelic exchange provide genetic evidence for the essential role of α‐toxin in Clostridium perfringens‐mediated gas gangrene. Molecular Microbiology. 15: 191-202. doi: 10.1111/j.1365-2958.1995.tb02234.x
  4. Batah, J.; Kobeissy, H.; Pham, P. T. B.; Denève-Larrazet, C.; Kuehne, S.; Collignon, A.; Janoir-Jouveshomme, C.; Marvaud, J. C.; Kansau, I. (2017). Clostridium difficile flagella induce a pro-inflammatory response in intestinal epithelium of mice in cooperation with toxins. Scientific Reports. 7: 1-10. doi: 10.1038/s41598-017-03621-z
  5. Borriello, S. P.; Carman, R. J. (1983). Association of iota-like toxin and Clostridium spiroforme with both spontaneous and antibiotic-associated diarrhea and colitis in rabbits. Journal of Clinical Microbiology. 17 (3): 414-418. doi: 0095-1137/83/030414-05$02.00/0
  6. Brandi, I. V.; Mozzer, O. D.; Vander Jorge, E.; Passos, F. J. V.; Passos, F. M. L.; Cangussu, A. S. R.; Sobrinho, E. M. (2014). Growth conditions of clostridium perfringens type B for production of toxins used to obtain veterinary vaccines. Bioprocess and biosystems engineering. 37 (9): 1737-1742. doi: 10.1007/s00449-014-1146-0
  7. Brandi, I. V.; Santos, E. M. S.; de Carvalho, B. M. A.; Durães, C. A. F.; Farias, P. K. S.; Sari, R. S.; Junior, A. P. (2016). Total combining power: Technique for the evaluation of the quality control process of clostridiosis vaccines. Journal of microbiological methods. 130: 164-168. doi: 10.1016/j.mimet.2016.08.023
  8. Carman, R. J.; Borriello, S. P. (1984). Infectious nature of Clostridium spiroforme-mediated rabbit enterotoxaemia. Veterinary microbiology. 9 (5): 497-502. doi: 10.1016/0378-1135(84)90070-1
  9. Chakravorty, A.; Awad, M. M.; Hiscox, T. J.; Cheung, J. K.; Choo, J. M.; Lyras, D.; Rood, J. I. (2014). Opioid analgesics stop the development of clostridial gas gangrene. Journal of Infectious Diseases. 210: 483-492. doi: 10.1093/infdis/jiu101
  10. Diab, S. S.; Kinde, H.; Moore, J.; Shahriar, M. F.; Odani, J.; Anthenill, L.; Uzal, F. A. (2012). Pathology of Clostridium perfringens type C enterotoxemia in horses. Veterinary Pathology. 49 (2): 255-263. doi: 10.1177/0300985811404710
  11. Domenighini, M.; Rappuoli, R. (1996). Three conserved consensus sequences identify the NAD-binding site of ADP-ribosylating enzymes, expressed by eukaryotes, bacteria and T-even bacteriophages. Molecular Microbiology. 21: 667–674 doi: 10.1046/j.1365-2958.1996.321396.x
  12. Felix, M. K. C.; Deusdará, T. T.; Santos, L. S. S.; Aguiar, R. W. S.; Corrêa, R. F. T.; Brandi, I. V.; Cangussu, A. S. R. (2019). Inactivated alpha toxin from Clostridium novyi type B in nano-emulsion protect partially protects Swiss mice from lethal alpha toxin challenge. Scientific reports. 9 (1): 1-9. doi: 10.1038/s41598-019-50683-2
  13. Ferrarezi, M. C.; Cardoso, T. C.; Dutra, I. S. (2008). Genotyping of Clostridium perfringens isolated from calves with neonatal diarrhea. Anaerobe. 14: 328-331. doi: 10.1016/j.anaerobe.2008.12.001
  14. Filho, E. J. F.; Carvalho, A. U.; Assis, R. A.; Lobato, F. F.; Rachid, M. A.; Carvalho, A. A.; Ferreira, P. M.; Nascimento, R. A.; Fernandes, A. A.; Vidal, J. E.; Uzal, F. A. (2009). Clinicopathologic features of experimental Clostridium perfringens type D enterotoxemia in cattle. Veterinary Pathology. 46: 1213-1220. doi: 10.1354/vp.08-VP-0304-U-FL
  15. Fleming, S. (1985). Enterotoxemia in neonatal calves. Veterinary Clinics of North America: Food Animal Practice. 1 (3): 509-514. doi: 10.1016/S0749-0720(15)31299-8
  16. Freedman, J. C.; Theoret, J. R.; Wisniewski, J. A.; Uzal, F. A.; Rood, J. I.; McClane, B.A. (2015). Clostridium perfringens type A–E toxin plasmids. Research in Microbiology. 166: 264-279. doi: 10.1016/j.resmic.2014.09.004
  17. Fuentes, L.; Lebenkoff, S.; White, K.; Gerdts, C.; Hopkins, K.; Potter, J. E.; Grossman, D.; Project, P. E.; Sciences, R. (2016). Animal models to study the pathogenesis of human Clostridium perfringens infections. Veterinary Microbiology. 93: 292-297. doi: 10.1016/j.vetmic.2015.02.013.Animal
  18. Gibert, M.; Marvaud, J. C.; Pereira, Y.; Hale, M. L.; Stiles, B. G.; Boquet, P.; Lamaze, C.; Popoff, M. R. (2007). Differential requirement for the translocation of clostridial binary toxins: Iota toxin requires a membrane potential gradient. FEBS Letters. 581: 1287-1296. doi: 10.1016/j.febslet.2007.02.041
  19. Gibert, M.; Monier, M. N.; Ruez, R.; Hale, M. L.; Stiles, B. G.; Benmerah, A.; Johannes, L.; Lamaze, C.; Popoff, M. R. (2011). Endocytosis and toxicity of clostridial binary toxins depend on a clathrin-independent pathway regulated by Rho-GDI. Cellular Microbiology. 13: 154-170. doi: 10.1111/j.1462-5822.2010.01527.x
  20. Gibert, M.; Petit, L.; Raffestin, S.; Okabe, A.; Popoff, M. R. (2000). Clostridium perfringens iota-toxin requires activation of both binding and enzymatic components for cytopathic activity. Infection and Immunity. 68: 3848–3853. doi: 10.1128/IAI.68.7.3848-3853.2000
  21. Ghoneim, N. H.; Hamza, D. A. (2017). Epidemiological studies on Clostridium perfringens food poisoning in retail foods. Rev. Sci. Tech. 36 (3): 1025-1032. doi: 10.20506/rst.36.3.2734
  22. Harada, M.; Kondoh, M.; Ebihara, C.; Takahashi, A.; Komiya, E.; Fujii, M.; Mizuguchi, H.; Tsunoda, S. I.; Horiguchi, Y.; Yagi, K.; Watanabe, Y. (2007). Role of tyrosine residues in modulation of claudin-4 by the C-terminal fragment of Clostridium perfringens enterotoxin. Biochemical Pharmacology. 73: 206-214. doi: 10.1016/j.bcp.2006.10.002
  23. Harkness, J. M.; Li, J.; McClane, B. A. (2012). Identification of a lambda toxin-negative Clostridium perfringens strain that processes and activates epsilon prototoxin intracellularly. Anaerobe. 18: 546-552. doi: 10.1016/j.anaerobe.2012.09.001
  24. Ismail, Z. B; Omoush, F. (2019). Abomasal displacement in neonatal dairy calves: Review of recent literature with special emphasis on abomasal torsion. Veterinary World. 12: 1121-1125. doi: 10.14202/vetworld.2019.1121-1125
  25. Jewell, S. A.; Titball, R. W.; Huyet, J.; Naylor, C. E.; Basak, A. K.; Gologan, P.; Winlove, C. P.; Petrov, P. G. (2015). Clostridium perfringens α-toxin interaction with red cells and model membranes. Soft Matter. 11: 7748-7761. doi: 10.1039/c5sm00876j
  26. Keyburn, A. L.; Yan, X. X.; Bannam, T. L.; Van Immerseel, F.; Rood, J. I.; Moore, R. J. (2010). Association between avian necrotic enteritis and Clostridium perfringens strains expressing NetB toxin. Veterinary Research. 41. doi: 10.1051/vetres/2009069
  27. Kim, H.; Byun, J.; Roh, I.; Bae, Y.; Lee, M.; Kim, B.; Songer, J. G.; Jung, B. Y. (2013). First isolation of Clostridium perfringens type E from a goat with diarrhea. Anaerobe. 22: 141-143. doi: 10.1016/j.anaerobe.2013.06.009
  28. Knapp, O.; Benz, M.; Popoff, R. (2016). Pore-forming activity of clostridial binary toxins. Biochimica et Biophysica Acta - Biomembranes. 1858: 512-525. doi: 10.1016/j.bbamem.2015.08.006
  29. Knapp, O.; Maier, E.; Benz, R.; Geny, B.; Popoff, M. R. (2009). Identification of the channel-forming domain of Clostridium perfringens Epsilon-toxin (ETX). Biochimica et Biophysica Acta - Biomembranes. 1788: 2584-2593. doi: 10.1016/j.bbamem.2009.09.020
  30. Li, J.; Adams, V.; Bannam, T. L.; Miyamoto, K.; Garcia, J. P.; Uzal, F. A.; Rood, J. I.; McClane, B. A. (2013). Toxin Plasmids of Clostridium perfringens. Microbiology and Molecular Biology Reviews. 77: 208-233. doi: 10.1128/mmbr.00062-12
  31. Lobato, F. C. F.; Moro, E.; Umehara, O.; Assis, R. A.; Martins, N. E.; Gonçalves, L. C. B. (2000). Avaliação da resposta de antitoxinas beta e épsilon de Clostridium perfringens induzidas em bovinos e coelhos por seis vacinas comerciais no Brasil. Arquivo Brasileiro de Medicina Veterinária e Zootecnia. 52 (4): 313-318. doi: 10.1590/S0102-09352000000400004
  32. Lobato, F. C. F.; Salvarani, F. M.; Gonçalves, L. A.; Pires, P. S.; Silva, R. O. S.; Alves, G. G.; Pereira, P. L. L. (2013). Clostridioses dos animais de produção. Veterinaria e zootecnia. 20: 29-48.
  33. Manteca, C.; Daube, G.; Jauniaux, T.; Linden, A.; Pirson, V.; Detilleux, J.; Ginter, A.; Coppe, P.; Kaeckenbeeck, A.; Mainil, J. G. (2002). A role for the Clostridium perfringens beta2 toxin in bovine enterotoxaemia? Veterinary microbiology. 86: 191-202. doi: 10.1016/s0378-1135(02)00008-1
  34. Mehdizadeh-Gohari, I.; Navarro, M. A.; Li, J.; Shrestha, A.; Uzal, F.; McClane, B. A. (2021). Pathogenicity and virulence of Clostridium perfringens. Virulence. 12: 723-753. doi: 10.1080/21505594.2021.1886777
  35. Miclard, J.; Jäggi, M.; Sutter, E.; Wyder, M.; Grabscheid, B.; Posthaus, H. (2009a). Clostridium perfringens beta-toxin targets endothelial cells in necrotizing enteritis in piglets. Veterinary Microbiology. 137: 320-325. doi: 10.1016/j.vetmic.2009.01.025
  36. Miclard, J.; Van-Baarlen, J.; Wyder, M.; Grabscheid, B.; Posthaus, H. (2009b). Clostridium perfringens β-toxin binding to vascular endothelial cells in a human case of enteritis necroticans. Journal of Medical Microbiology. 58: 826-828. doi: 10.1099/jmm.0.008060-0
  37. Minami, J.; Katayama, S.; Matsushita, O.; Matsushita, C.; Okabe, A. (1997). Lambda-toxin of Clostridium perfringens activates the precursor of epsilon-toxin by releasing its N- and C-terminal peptides. Microbiology and Immunology. 41: 527-535. doi: 10.1111/j.1348-0421.1997.tb01888.x
  38. Miyashiro, S.; Baldassi, L.; Nassar, A. (2009). Genotyping of Clostridium perfringens associated with sudden death in cattle. Journal of Venomous Animals and Toxins including Tropical Diseases. 15: 12-14. doi: 10.1590/S1678-91992009000300010
  39. Moreira, G. M. S. G.; Salvarani, F. M.; Da-Cunha, C. E. P.; Mendonça, M.; Moreira, Â. N.; Gonçalves, L. A.; Conceição, F. R. (2016). Immunogenicity of a trivalent recombinant vaccine against Clostridium perfringens alpha, beta, and epsilon toxins in farm ruminants. Scientific reports. 6 (1): 1-9. doi: 10.1038/srep22816
  40. Nagahama, M.; Nagayasu, K.; Kobayashi, K.; Sakurai, J. (2002). Binding component of Clostridium perfringens iota-toxin induces endocytosis in vero cells. Infection and Immunity. 70: 1909-1914. doi: 10.1128/IAI.70.4.1909-1914.2002
  41. Nagahama, M.; Sakaguchi, Y.; Kobayashi, K.; Ochi, S.; Sakurai, J. (2000). Characterization of the enzymatic component of Clostridium perfringens iota-toxin. Journal of Bacteriology. 182: 2096-2103. doi: 10.1128/JB.182.8.2096-2103.2000
  42. Nagahama, M.; Umezaki, M.; Tashiro, R.; Oda, M.; Kobayashi, K.; Shibutani, M.; Takagishi, T.; Ishidoh, K.; Fukuda, M.; Sakurai, J. (2012). Intracellular trafficking of Clostridium perfringens iota-toxin b. Infection and Immunity. 80: 3410-3416. doi: 10.1128/IAI.00483-12
  43. Navarro, M. A.; McClane, B. A.; Uzal, F. A. (2018). Mechanisms of action and cell death associated with Clostridium perfringens toxins. Toxins. 10: 1-21. doi: 10.3390/toxins10050212
  44. Navarro, M. A.; Shrestha, A.; Freedman, J. C.; Beingesser, J.; McClane, B. A.; Uzal, F. A. (2019). Potential therapeutic effects of mepacrine against clostridium perfringens enterotoxin in a mouse model of enterotoxemia. Infection and Immunity. 87: 1-10. doi: 10.1128/IAI.00670-18
  45. Park, M.; Deck, J.; Foley, S. L.; Nayak, R.; Songer, J. G.; Seibel, J. R.; Rafii, F. (2016). Diversity of Clostridium perfringens isolates from various sources and prevalence of conjugative plasmids. Anaerobe. 38: 25-35. doi: 10.1016/j.anaerobe.2015.11.003
  46. Perelle, S.; Domenighini, M.; Popoff, M. R. (1996). Evidence that Arg-295, Glu-378, and Glu-380 are active-site residues of the ADP-ribosyltransferase activity of iota toxin. FEBS Letters. 395: 191-194. doi: 10.1016/0014-5793(96)01035-6
  47. Prescott, J. F.; Parreira, V. R.; Mehdizadeh-Gohari, I.; Lepp, D.; Gong, J. (2016). The pathogenesis of necrotic enteritis in chickens: what we know and what we need to know: a review. Avian Pathology. 45: 288-294. doi: 10.1080/03079457.2016.1139688
  48. Redondo, L. M.; Carrasco, J. M. D.; Redondo, E. A.; Delgado, F.; Fernández-Miyakawa, M. E. (2015). Clostridium perfringens type E virulence traits involved in gut colonization. PLoS ONE. 10: 1-18. doi: 10.1371/journal.pone.0121305
  49. Redondo, L. M.; Farber, M.; Venzano, A.; Jost, B. H.; Parma, Y. R.; Fernandez-Miyakawa, M. E. (2013). Sudden death syndrome in adult cows associated with Clostridium perfringens type E. Anaerobe. 20: 1-4. doi: 10.1016/j.anaerobe.2013.01.001
  50. Redondo, L. M.; Redondo, E. A.; Dailoff, G. C.; Leiva, C. L.; Diaz-Carrasco, J. M.; Bruzzone, O. A.; Cangelosi, A.; Geoghegan, P.; Fernandez-Miyakawa, M. E. (2017). Effects of Clostridium perfringens iota toxin in the small intestine of mice. Anaerobe. 48: 83-88. doi: 10.1016/j.anaerobe.2017.07.007
  51. Richard, J. F.; Mainguy, G.; Gibert, M.; Marvaud, J. C.; Stiles, B. G.; Popoff, M. R. (2002). Transcytosis of iota-toxin across polarized CaCo-2 cells. Molecular Microbiology. 43: 907-917. doi: 10.1046/j.1365-2958.2002.02806.x
  52. Rood, J. I.; Adams, V.; Lacey, J.; Lyras, D.; McClane, B. A.; Melville, S. B.; Moore, R. J.; Popoff, M. R.; Sarker, M. R.; Songer, J. G.; Uzal, F. A.; Van-Immerseel, F. (2018). Expansion of the Clostridium perfringens toxin-based typing scheme. Anaerobe. 53: 5-10. doi: 10.1016/j.anaerobe.2018.04.011
  53. Rood, J. I.; Keyburn, A. L.; Moore, R. J. (2016). NetB and necrotic enteritis: the hole movable story. Avian Pathology. 45: 295-301. doi: 10.1080/03079457.2016.1158781
  54. Sakurai, J.; Nagahama, M.; Oda, M.; Tsuge, H.; Kobayashi, K. (2009). Clostridium perfringens iota-toxin: structure and function. Toxins. 1: 208-228. doi: 10.3390/toxins1020208
  55. Santana, J. A.; Ferreira, A. C. D. A.; Souza, M. D. C. C. D.; Moreira, M. A. S.; Lima, M. C.; Cruz, D. S. G.; Lobato, F. C. F.; Silva, R. O. S. (2018). Isolation and genotyping of clostridium perfringens from goats in Minas Gerais, Brazil. Ciencia Rural. 48: 5-8. doi: 10.1590/0103-8478cr20180101
  56. Sari, R. S.; Almeida, A. C.; Cangussu, A. S. R.; Jorge, E. V.; Mozzer, D. O.; Santos, H. O.; Quintilio, W.; Brandi, I. V.; Andrade, V. A.; Miguel, A. S. M.; Santos, E. M. S. (2016). Anti-botulism single-shot vaccine using chitosan for protein encapsulation by simple coacervation. Anaerobe. 42: 182-187.
  57. Sayeed, S.; Uzal, F. A.; Fisher, D. J.; Saputo, J.; Vidal, J. E.; Chen, Y., Gupta, P.; Rood, J. I.; McClane, B. A. (2008). Beta toxin is essential for the intestinal virulence of Clostridium perfringens type C disease isolate CN3685 in a rabbit ileal loop model. Molecular Microbiology. 67: 15-30. doi: 10.1111/j.1365-2958.2007.06007.x
  58. Schmidt, G.; Papatheodorou, P.; Aktories, K. (2015). Novel receptors for bacterial protein toxins. Current Opinion in Microbiology. 23: 55-61. doi: 10.1016/j.mib.2014.11.003
  59. Schumacher, V. L.; Martel, A.; Pasmans, F.; van-Immerseel, F.; Posthaus, H. (2013). Endothelial binding of beta toxin to small intestinal mucosal endothelial cells in early stages of experimentally induced Clostridium perfringens type C enteritis in pigs. Veterinary Pathology. 50: 626-629. doi: 10.1177/0300985812461362
  60. Shrestha, A.; Uzal, F. A.; McClane, B. A. (2019). Enterotoxic Clostridia: Clostridium perfringens Enteric Diseases. Gram-Positive Pathogens. 6: 977-990. doi: 10.1128/9781683670131.ch60
  61. Silva, R. O. S.; Lobato, F. C. F. (2015). Clostridium perfringens: A review of enteric diseases in dogs, cats and wild animals. Anaerobe. 33: 14-17. doi: 10.1016/j.anaerobe.2015.01.006
  62. Silva, R. O. S.; Oliveira-Junior, C. A.; Guedes, R. M. C.; Lobato, F. C. F. (2015). Clostridium perfringens: a review of the disease in pigs, horses and broiler chickens. Ciência Rural. 45: 1027-1034. doi: 10.1590/0103-8478cr20140927
  63. Simpson, K. M.; Callan, R. J.; Van-Metre, D. C. (2018). Clostridial Abomasitis and Enteritis in Ruminants. Veterinary Clinics of North America: Food Animal Practice. 34: 155-184. doi: 10.1016/j.cvfa.2017.10.010
  64. Smedley, J. G.; McClane, B. A. (2004). Fine mapping of the N-terminal cytotoxicity region of Clostridium perfringens enterotoxin by site-directed mutagenesis. Infection and Immunity. 72: 6914-6923. doi: 10.1128/IAI.72.12.6914-6923.2004
  65. Sobrinho, E. M.; Almeida, A. C.; Brandi, I. V.; Colen, F.; Lobato, F. C. F.; Cangussu, A. S. R.; Quintilio, W.; Santos, H. O.; Sari, R. S. (2014). ELISA and modified toxin-binding inhibition test for quality control of the clostridial vaccine processes. Arquivo Brasileiro de Medicina Veterinaria e Zootecnia. 66: 713-720. doi: 10.1590/1678-41625407
  66. Sobrinho, E. M.; Cangussu, A. S. R.; Brandi, I. V.; Sari, R. S.; Almeida, A. C.; Colen,F.; Quintilio, W.; Santos, H. O. (2010). Modified toxin-binding inhibition (ToBI) test for epsilon antitoxin determination in serum of immunized rabbits. Veterinary Immunology and Immunopathology. 138: 129-133. doi: 10.1016/j.vetimm.2010.07.007
  67. Songer, J. G. (1996). Clostridial enteric diseases of domestic animals. Clinical Microbiology Reviews. 9: 216-234. doi: 10.1128/cmr.9.2.216
  68. Songer, J. G.; Miskimmins, D. W. (2004). Clostridium perfringens type E enteritis in calves: Two cases and a brief review of the literature. Anaerobe. 10: 239-242. doi: 10.1016/j.anaerobe.2004.05.001
  69. Stiles, B. G.; Wilkins, T. D. (1986). Purification and characterization of Clostridium perfringens iota toxin: Dependence on two nonlinked proteins for biological activity. Infection and Immunity. 54: 683-688. doi: 10.1128/iai.54.3.683-688.1986
  70. Szklarczyk D, Gable A.L.; Nastou, K.C.; Lyon, D.; Kirsch, R.; Pyysalo, S.; Doncheva, N.T.; Legeay, M.; Fang, T.; Bork, P.; Jensen, L.J.; von Mering, C. (2021). The STRING database in 2021: customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 2021 Jan 8;49(D1):D605-12
  71. Takahashi, A.; Komiya, E.; Kakutani, H.; Yoshida, T.; Fujii, M.; Horiguchi, Y.; Mizuguchi, H.; Tsutsumi, Y.; ichi-Tsunoda, S.; Koizumi, N.; Isoda, K.; Yagi, K.; Watanabe, Y.; Kondoh, M. (2008). Domain mapping of a claudin-4 modulator, the C-terminal region of C-terminal fragment of Clostridium perfringens enterotoxin, by site-directed mutagenesis. Biochemical Pharmacology. 75: 1639-1648. doi: 10.1016/j.bcp.2007.12.016
  72. Takehara, M.; Takagishi, T.; Seike, S.; Oda, M.; Sakaguchi, Y.; Hisatsune, J.; Ochi, S.; Kobayashi, K.; Nagahama, M. (2017). Cellular entry of Clostridium perfringens iota-toxin and Clostridium botulinum C2 toxin. Toxins. 9: 8-11. doi: 10.3390/toxins9080247
  73. Tsuge, H.; Nagahama, M.; Nishimura, H.; Hisatsune, J.; Sakaguchi, Y.; Itogawa, Y.; Katunuma, N.; Sakurai, J. (2003). Crystal structure and site-directed mutagenesis of enzymatic components from Clostridium perfringens Iota-toxin. Journal of Molecular Biology. 325: 471-483. doi: 10.1016/S0022-2836(02)01247-0
  74. Tsuge, H.; Nagahama, M.; Oda, M.; Iwamoto, S.; Utsunomiya, H.; Marquez, V. E.; Katunuma, N.; Nishizawa, M.; Sakurai, J. (2008). Structural basis of actin recognition and arginine ADP-ribosylation by Clostridium perfringens ι-toxin. Proceedings of the National Academy of Sciences of the United States of America. 105: 7399-7404. doi: 10.1073/pnas.0801215105
  75. Uzal, F. A. (2004). Diagnosis of Clostridium perfringens intestinal infections in sheep and goats. Anaerobe. 10: 135-143. doi: 10.1016/j.anaerobe.2003.08.005
  76. Uzal, F. A.; Kelly, W. R. (1997). Effects of the intravenous administration of Clostridium perfringens type D epsilon toxin on young goats and lambs. Journal of Comparative Pathology. 116: 63-71. doi: 10.1016/S0021-9975(97)80044-8
  77. Uzal, F. A.; Navarro, M. A.; Li, J.; Freedman, J. C.; Shrestha, A.; McClane, B. A. (2018). Comparative pathogenesis of enteric clostridial infections in humans and animals. Anaerobe. 53: 11-20. doi: 10.1016/j.anaerobe.2018.06.002
  78. Uzal, F. A.; Sentíes-Cué, C. G.; Rimoldi, G.; Shivaprasad, H. L. (2016). Non- Clostridium perfringens infectious agents producing necrotic enteritis-like lesions in poultry. Avian Pathology. 45: 326-333. doi: 10.1080/03079457.2016.1159282
  79. Uzal, F. A.; Vidal, J. E.; McClane, B. A.; Gurjar, A. A. (2010). Clostridium Perfringens Toxins Involved in Mammalian Veterinary Diseases. The open toxinology journal. 2: 24-42. doi: 10.2174/1875414701003010024
  80. Van Itallie, C. M.; Betts, L.; Smedley, J. G.; McClane, B. A.; Anderson, J. M. (2008). Structure of the Claudin-binding domain of Clostridium perfringens enterotoxin. Journal of Biological Chemistry. 283: 268-274. doi: 10.1074/jbc.M708066200
  81. Vidal, J. E.; Ohtani, K.; Shimizu, T.; McClane, B. A. (2009). Contact with enterocyte-like Caco-2 cells induces rapid upregulation of toxin production by Clostridium perfringens type C isolates. Cellular Microbiology. 11: 1306-1328. doi: 10.1111/j.1462-5822.2009.01332.x
  82. Waters, M.; Raju, D.; Garmory, H. S.; Popoff, M. R.; Sarker, M. R. (2005). Regulated expression of the beta2-toxin gene (cpb2) in Clostridium perfringens type A isolates from horses with gastrointestinal diseases. Journal of Clinical Microbiology. 43: 4002-4009. doi: 10.1128/JCM.43.8.4002-4009.2005
  83. Wigelsworth, D. J.; Ruthel, G.; Schnell, L.; Herrlich, P.; Blonder, J.; Veenstra, T. D.; Carman, R. J.; Wilkins, T. D.; Van-Nhieu, G. T.; Pauillac, S.; Gibert, M.; Sauvonnet, N.; Stiles, B. G.; Popoff, M. R.; Barth, H. (2012). CD44 Promotes Intoxication by the Clostridial Iota-Family Toxins. PLoS ONE. 7: e51356. doi: 10.1371/journal.pone.0051356
  84. Yamada, T.; Yoshida, T.; Kawamoto, A.; Mitsuoka, K.; Iwasaki, K.; Tsuge, H. (2020). Cryo-EM structures reveal translocational unfolding in the clostridial binary iota toxin complex. Nature Structural & Molecular Biology. 27: 288-296. doi: 10.1038/s41594-020-0388-6

Downloads

Download data is not yet available.