Advertisement

Clostridium perfringens Epsilon Toxin: Structural and Mechanistic Insights

Reference work entry
First Online:
  • 1k Downloads
Part of the Toxinology book series (TOXI)

Abstract

Epsilon toxin (ETX) is produced by strains of Clostridium perfringens classified as type B or D. ETX belongs to the heptameric β-pore-forming toxins including Aeromonas aerolysin and Clostridium septicum alpha toxin, which are characterized by the formation of a pore through the plasma membrane of eukaryotic cells and containing a β-barrel composed of 14 amphipathic β-strands. In contrast to aerolysin and C. septicum alpha toxin, ETX is a much more potent toxin, which is responsible for enterotoxemia in animals, mainly in sheep. ETX induces perivascular edema in various tissues and accumulates particularly in the kidneys and in the brain, where it causes edema and necrotic lesions. ETX is able to pass through the blood-brain barrier (BBB) and to stimulate the release of glutamate, which accounts for the nervous excitation symptoms observed in animal enterotoxemia. At the cellular level, ETX causes a rapid swelling followed by a cell death involving necrosis. Recently, ETX has been found to induce demyelination and could be involved in demyelinating diseases like multiple sclerosis. The precise mode of action of ETX remains undetermined.

Keywords

Epsilon toxin Clostridium perfringens Pore-forming toxin Myelin Neurotoxicity Multiple sclerosis 
This is a preview of subscription content, log in to check access.

References

  1. Banks WA. Characteristics of compounds that cross the blood-brain barrier. BMC Neurol. 2009;9 Suppl 1:S3.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Bokori-Brown M, Kokkinidou MC, Savva CG, Fernandes da Costa S, Naylor CE, Cole AR, Moss DS, Basak AK, Titball RW. Clostridium perfringens epsilon toxin H149A mutant as a platform for receptor binding studies. Protein Sci. 2013;22(5):650–9.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Bokori-Brown M, Hall CA, Vance C, Fernandes da Costa SP, Savva CG, Naylor CE, Cole AR, Basak AK, Moss DS, Titball RW. Clostridium perfringens epsilon toxin mutant Y30A-Y196A as a recombinant vaccine candidate against enterotoxemia. Vaccine. 2014;32(23):2682–7.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Borrmann E, Günther H, Köhler H. Effect of Clostridium perfringens epsilon toxin on MDCK cells. FEMS Immunol Med Microbiol. 2001;31:85–92.CrossRefPubMedGoogle Scholar
  5. Briggs DC, Naylor CE, Smedley 3rd JG, Lukoyanova N, Robertson S, Moss DS, McClane BA, Basak AK. Structure of the food-poisoning Clostridium perfringens enterotoxin reveals similarity to the aerolysin-like pore-forming toxins. J Mol Biol. 2011;413(1):138–49.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Buxton D, Morgan KT. Studies of lesions produced in the brains of colostrum deprived lambs by Clostridium welchii (Cl. perfringens) type D toxin. J Comp Pathol. 1976;86(3):435–47.CrossRefPubMedGoogle Scholar
  7. Chassin C, Bens M, de Barry J, Courjaret R, Bossu JL, Cluzeaud F, Ben Mkaddem S, Gibert M, Poulain B, Popoff MR, Vandewalle A. Pore-forming epsilon toxin causes membrane permeabilization and rapid ATP depletion-mediated cell death in renal collecting duct cells. Am J Physiol Renal Physiol. 2007;293(3):F927–37.CrossRefPubMedGoogle Scholar
  8. Chen J, McClane BA. Role of the agr-like quorum sensing system in regulating toxin production by Clostridium perfringens type B strains CN1793 and CN1795. Infect Immun. 2012;80:3008–17.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Cole AR, Gibert M, Popoff MR, Moss DS, Titball RW, Basak A. Clostridium perfringens ε-toxin shows structural similarity to the pore-forming toxin aerolysin. Nat Struct Mol Biol. 2004;11:797–8.CrossRefPubMedGoogle Scholar
  10. Degiacomi MT, Iacovache I, Pernot L, Chami M, Kudryashev M, Stahlberg H, van der Goot FG, Dal Peraro M. Molecular assembly of the aerolysin pore reveals a swirling membrane-insertion mechanism. Nat Chem Biol. 2013;9(10):623–9.CrossRefPubMedGoogle Scholar
  11. Dorca-Arevalo J, Soler-Jover A, Gibert M, Popoff MR, Martin-Satue M, Blasi J. Binding of epsilon-toxin from Clostridium perfringens in the nervous system. Vet Microbiol. 2008;131(1–2):14–25.CrossRefPubMedGoogle Scholar
  12. Dorca-Arevalo J, Martin-Satue M, Blasi J. Characterization of the high affinity binding of epsilon toxin from Clostridium perfringens to the renal system. Vet Microbiol. 2012;157:179–89.CrossRefPubMedGoogle Scholar
  13. Fennessey CM, Ivie SE, McClain MS. Coenzyme depletion by members of the aerolysin family of pore-forming toxins leads to diminished ATP levels and cell death. Mol Biosyst. 2012a;8(8):2097–105.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Fennessey CM, Sheng J, Rubin DH, McClain MS. Oligomerization of Clostridium perfringens epsilon toxin is dependent upon caveolins 1 and 2. PLoS One. 2012b;7(10):e46866.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Fernandez Miyakawa ME, Uzal FA. The early effects of Clostridium perfringens type D epsilon toxin in ligated intestinal loops of goats and sheep. Vet Res Commun. 2003;27(3):231–41.CrossRefPubMedGoogle Scholar
  16. Fernandez Miyakawa ME, Zabal O, Silberstein C. Clostridium perfringens epsilon toxin is cytotoxic for human renal tubular epithelial cells. Hum Exp Toxicol. 2011;30:275–82.CrossRefPubMedGoogle Scholar
  17. Ferrarezi MC, Curci VC, Cardoso TC. Cellular vacuolation and mitochondrial-associated factors induced by Clostridium perfringens epsilon toxin detected using acoustic flow cytometry. Anaerobe. 2013;24:55–9.CrossRefPubMedGoogle Scholar
  18. Finnie JW. Histopathological changes in the brain of mice given Clostridium perfringens type D epsilon toxin. J Comp Pathol. 1984a;94(3):363–70.CrossRefPubMedGoogle Scholar
  19. Finnie JW. Ultrastructural changes in the brain of mice given Clostridium perfringens type D epsilon toxin. J Comp Pathol. 1984b;94(3):445–52.CrossRefPubMedGoogle Scholar
  20. Finnie JW. Neurological disorders produced by Clostridium perfringens type D epsilon toxin. Anaerobe. 2004;10(2):145–50.CrossRefPubMedGoogle Scholar
  21. Finnie JW, Blumbergs PC, Manavis J. Neuronal damage produced in rat brains by Clostridium perfringens type D epsilon toxin. J Comp Pathol. 1999;120(4):415–20.CrossRefPubMedGoogle Scholar
  22. Garcia JP, Adams V, Beingesser J, Hughes ML, Poon R, Lyras D, Hill A, McClane BA, Rood JI, Uzal FA. Epsilon toxin is essential for the virulence of Clostridium perfringens type D infection in sheep, goats, and mice. Infect Immun. 2013;81(7):2405–14.CrossRefPubMedPubMedCentralGoogle Scholar
  23. Garcia JP, Beingesser J, Bohorov O, Bohorova N, Goodman C, Kim D, Pauly M, Velasco J, Whaley K, Zeitlin L, Roy CJ, Uzal FA. Prevention and treatment of Clostridium perfringens epsilon toxin intoxication in mice with a neutralizing monoclonal antibody (c4D7) produced in Nicotiana benthamiana. Toxicon. 2014;88:93–8.CrossRefPubMedGoogle Scholar
  24. Geny B, Popoff MR. Bacterial protein toxins and lipids: pore formation or toxin entry into cells. Biol Cell. 2006;98:667–78.CrossRefPubMedGoogle Scholar
  25. Gil C, Dorca-Arevalo J, Blasi J. Clostridium perfringens epsilon toxin binds to membrane lipids and its cytotoxic action depends on sulfatide. PLoS One. 2015;10(10):e0140321.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Gill DM. Bacterial toxins: lethal amounts. In: Laskin AI, Lechevalier HA, editors. Toxins and enzymes, vol. 8. Cleveland: CRC Press; 1987. p. 127–35.Google Scholar
  27. Gordon VM, Nelson KL, Buckley JT, Stevens VL, Tweten RK, Elwood PC, Leppla SH. Clostridium septicum alpha-toxin uses glycosylphosphatidylinositol-anchored protein receptors. J Biol Chem. 1999;274:27274–80.CrossRefPubMedGoogle Scholar
  28. Gurjar A, Li J, McClane BA. Characterization of toxin plasmids in Clostridium perfringens type C isolates. Infect Immun. 2010;78(11):4860–9.CrossRefPubMedPubMedCentralGoogle Scholar
  29. Hirschberg H, Zhang MJ, Gach HM, Uzal FA, Peng Q, Sun CH, Chighvinadze D, Madsen SJ. Targeted delivery of bleomycin to the brain using photo-chemical internalization of Clostridium perfringens epsilon prototoxin. J Neurooncol. 2009;95:317–29.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Hunter SE, Clarke IN, Kelly DC, Titball RW. Cloning and nucleotide sequencing of the Clostridium perfringens epsilon-toxin gene and its expression in Escherichia coli. Infect Immun. 1992;60:102–10.PubMedPubMedCentralGoogle Scholar
  31. Ivie SE, Fennessey CM, Sheng J, Rubin DH, McClain MS. Gene-trap mutagenesis identifies mammalian genes contributing to intoxication by Clostridium perfringens epsilon-toxin. PLoS One. 2011;6(3):e17787.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Justin N, Walker N, Bullifent HL, Songer G, Bueschel DM, Jost H, Naylor C, Miller J, Moss DS, Titball RW, Basak AK. The first strain of Clostridium perfringens isolated from an avian source has an alpha-toxin with divergent structural and kinetics properties. Biochemistry. 2002;41:6253–62.CrossRefPubMedGoogle Scholar
  33. Kitadokoro K, Nishimura K, Kamitani S, Fukui-Miyazaki A, Toshima H, Abe H, Kamata Y, Sugita-Konishi Y, Yamamoto S, Karatani H, Horiguchi Y. Crystal structure of Clostridium perfringens enterotoxin displays features of beta-pore-forming toxins. J Biol Chem. 2011;286(22):19549–55.CrossRefPubMedPubMedCentralGoogle Scholar
  34. Knapp O, Maier E, Benz R, Geny B, Popoff MR. Identification of the channel-forming domain of Clostridium perfringens epsilon-toxin (ETX). Biochim Biophys Acta. 2009;1788(12):2584–93.CrossRefPubMedGoogle Scholar
  35. Knapp O, Maier E, Mkaddem SB, Benz R, Bens M, Chenal A, Geny B, Vandewalle A, Popoff MR. Clostridium septicum alpha-toxin forms pores and induces rapid cell necrosis. Toxicon. 2010a;55(1):61–72.CrossRefPubMedGoogle Scholar
  36. Knapp O, Stiles BG, Popoff MR. The aerolysin-like toxin family of cytolytic, pore-forming toxins. Open Toxinol J. 2010b;3:53–68.CrossRefGoogle Scholar
  37. Lewis M, Weaver CD, McClain MS. Identification of small molecule inhibitors of Clostridium perfringens epsilon-toxin cytotoxicity using a cell-based high-throughput screen. Toxins (Basel). 2010;2(7):1825–47.CrossRefGoogle Scholar
  38. Li Q, Xin W, Gao S, Kang L, Wang J. A low-toxic site-directed mutant of Clostridium perfringens epsilon-toxin as a potential candidate vaccine against enterotoxemia. Hum Vaccines Immunother. 2013;9(11):2386–92.CrossRefGoogle Scholar
  39. Li J, Freedman JC, McClane BA. NanI Sialidase, CcpA, and CodY work together to regulate epsilon toxin production by Clostridium perfringens type D strain CN3718. J Bacteriol. 2015;197(20):3339–53.CrossRefPubMedPubMedCentralGoogle Scholar
  40. Linden JR, Ma Y, Zhao B, Harris JM, Rumah KR, Schaeren-Wiemers N, Vartanian T. Clostridium perfringens epsilon toxin causes selective death of mature oligodendrocytes and central nervous system demyelination. MBio. 2015;6(3):e02513.CrossRefPubMedPubMedCentralGoogle Scholar
  41. Lindsay CD, Hambrook JL, Upshall DG. Examination of toxicity of Clostridium perfringens ε-toxin in the MDCK cell line. Toxicol In Vitro. 1995;9:213–8.CrossRefPubMedGoogle Scholar
  42. Lobato FC, Lima CG, Assis RA, Pires PS, Silva RO, Salvarani FM, Carmo AO, Contigli C, Kalapothakis E. Potency against enterotoxemia of a recombinant Clostridium perfringens type D epsilon toxoid in ruminants. Vaccine. 2010;28(38):6125–7.CrossRefPubMedGoogle Scholar
  43. Lonchamp E, Dupont JL, Wioland L, Courjaret R, Mbebi-Liegeois C, Jover E, Doussau F, Popoff MR, Bossu JL, de Barry J, Poulain B. Clostridium perfringens epsilon toxin targets granule cells in the mouse cerebellum and stimulates glutamate release. PLoS One. 2010;5(9):e13046.CrossRefPubMedPubMedCentralGoogle Scholar
  44. Manni MM, Sot J, Goni FM. Interaction of Clostridium perfringens epsilon-toxin with biological and model membranes: a putative protein receptor in cells. Biochim Biophys Acta. 2015;1848(3):797–804.CrossRefPubMedGoogle Scholar
  45. Mantis NJ. Vaccines against the category B toxins: Staphylococcal enterotoxin B, epsilon toxin and ricin. Adv Drug Deliv Rev. 2005;57(9):1424–39.CrossRefPubMedGoogle Scholar
  46. Masson JB, Casanova D, Turkcan S, Voisinne G, Popoff MR, Vergassola M, Alexandrou A. Inferring maps of forces inside cell membrane microdomains. Phys Rev Lett. 2009;102(4):048103.CrossRefPubMedGoogle Scholar
  47. Mathur DD, Deshmukh S, Kaushik H, Garg LC. Functional and structural characterization of soluble recombinant epsilon toxin of Clostridium perfringens D, causative agent of enterotoxaemia. Appl Microbiol Biotechnol. 2010;88(4):877–84.CrossRefPubMedGoogle Scholar
  48. Matute C. Glutamate and ATP signalling in white matter pathology. J Anat. 2011;219(1):53–64.CrossRefPubMedPubMedCentralGoogle Scholar
  49. Matute C, Domercq M, Sanchez-Gomez MV. Glutamate-mediated glial injury: mechanisms and clinical importance. Glia. 2006;53(2):212–24.CrossRefPubMedGoogle Scholar
  50. McClain MS, Cover TL. Functional analysis of neutralizing antibodies against Clostridium perfringens epsilon-toxin. Infect Immun. 2007;75(4):1785–93.CrossRefPubMedPubMedCentralGoogle Scholar
  51. Melton JA, Parker MW, Rossjohn J, Buckley JT, Tweten RK. The identification and structure of the membrane-spanning domain of the Clostridium septicum alpha toxin. J Biol Chem. 2004;279(14):14315–22.CrossRefPubMedGoogle Scholar
  52. Minami J, Katayama S, Matsushita O, Matsushita C, Okabe A. Lambda-toxin of Clostridium perfringens activates the precursor of epsilon-toxin by releasing its N- and C-terminal peptides. Microbiol Immunol. 1997;41:527–35.CrossRefPubMedGoogle Scholar
  53. Miyamoto O, Minami J, Toyoshima T, Nakamura T, Masada T, Nagao S, Negi T, Itano T, Okabe A. Neurotoxicity of Clostridium perfringens epsilon-toxin for the rat hippocampus via glutamanergic system. Infect Immun. 1998;66:2501–8.PubMedPubMedCentralGoogle Scholar
  54. Miyamoto O, Sumitami K, Nakamura T, Yamagani S, Miyatal S, Itano T, Negi T, Okabe A. Clostridium perfringens epsilon toxin causes excessive release of glutamate in the mouse hippocampus. FEMS Microbiol Lett. 2000;189:109–13.CrossRefPubMedGoogle Scholar
  55. Miyata S, Matsushita O, Minami J, Katayama S, Shimamoto S, Okabe A. Cleavage of C-terminal peptide is essential for heptamerization of Clostridium perfringens ε-toxin in the synaptosomal membrane. J Biol Chem. 2001;276:13778–83.CrossRefPubMedGoogle Scholar
  56. Miyata S, Minami J, Tamai E, Matsushita O, Shimamoto S, Okabe A. Clostridium perfringens ε-toxin forms a heptameric pore within the detergent-insoluble microdomains of Madin-Darby Canine Kidney Cells and rat synaptosomes. J Biol Chem. 2002;277:39463–8.CrossRefPubMedGoogle Scholar
  57. Mollby R, Holme T, Nord CE, Smyth CJ, Wadstrom T. Production of phospholipase C (alpha-toxin), haemolysins and lethal toxins by Clostridium perfringens types A to D. J Gen Microbiol. 1976;96(1):137–44.CrossRefPubMedGoogle Scholar
  58. Murrel TGC, O’Donoghue PJ, Ellis T. A review of the sheep-multiple sclerosis connection. Med Hypotheses. 1986;19:27–39.CrossRefGoogle Scholar
  59. Nagahama M, Sakurai J. Distribution of labeled Clostridium perfringens epsilon toxin in mice. Toxicon. 1991;29(2):211–7.CrossRefPubMedGoogle Scholar
  60. Nagahama M, Sakurai J. High-affinity binding of Clostridium perfringens epsilon-toxin to rat brain. Infect Immun. 1992;60(3):1237–40.PubMedPubMedCentralGoogle Scholar
  61. Nagahama M, Hara H, Fernandez-Miyakawa M, Itohayashi Y, Sakurai J. Oligomerization of Clostridium perfringens epsilon-toxin is dependent upon membrane fluidity in liposomes. Biochemistry. 2006;45(1):296–302.CrossRefPubMedGoogle Scholar
  62. Nagahama M, Itohayashi Y, Hara H, Higashihara M, Fukatani Y, Takagishi T, Oda M, Kobayashi K, Nakagawa I, Sakurai J. Cellular vacuolation induced by Clostridium perfringens epsilon-toxin. Febs J. 2011;278(18):3395–407.CrossRefPubMedGoogle Scholar
  63. Nestorovich EM, Karginov VA, Bezrukov SM. Polymer partitioning and ion selectivity suggest asymmetrical shape for the membrane pore formed by epsilon toxin. Biophys J. 2010;99(3):782–9.CrossRefPubMedPubMedCentralGoogle Scholar
  64. Odendaal MW, Visser JJ, Bergh N, Botha WJ. The effect of passive immunization on active immunity against Clostridium perfringens type D in lambs. Onderstepoort J Vet Res. 1989;56(4):251–5.PubMedGoogle Scholar
  65. Oyston PCF, Payne DW, Havard HL, Williamson ED, Titball RW. Production of a non-toxic site-directed mutant of Clostridium perfringens e-toxin which induces protective immunity in mice. Microbiology. 1998;144:333–41.CrossRefPubMedGoogle Scholar
  66. Parker MW, Buckley JT, Postma JP, Tucker AD, Leonard K, Pattus F, Tsernoglou D. Structure of the Aeromonas toxin proaerolysin in its water-soluble and membrane-channel states. Nature. 1994;367(6460):292–5.CrossRefPubMedGoogle Scholar
  67. Payne DW, Williamson ED, Havard H, Modi N, Brown J. Evaluation of a new cytotoxicity assay for Clostridium perfringens type D epsilon toxin. FEMS Microbiol Lett. 1994;116:161–8.CrossRefPubMedGoogle Scholar
  68. Pelish TM, McClain MS. Dominant-negative inhibitors of the Clostridium perfringens epsilon-toxin. J Biol Chem. 2009;284(43):29446–53.CrossRefPubMedPubMedCentralGoogle Scholar
  69. Petit L, Gibert M, Gillet D, Laurent-Winter C, Boquet P, Popoff MR. Clostridium perfringens epsilon-toxin acts on MDCK cells by forming a large membrane complex. J Bacteriol. 1997;179:6480–7.CrossRefPubMedPubMedCentralGoogle Scholar
  70. Petit L, Gibert M, Popoff MR. Clostridium perfringens: toxinotype and genotype. Trends Microbiol. 1999;7:104–10.CrossRefPubMedGoogle Scholar
  71. Petit L, Maier E, Gibert M, Popoff MR, Benz R. Clostridium perfringens epsilon-toxin induces a rapid change in cell membrane permeability to ions and forms channels in artificial lipid bilayers. J Biol Chem. 2001;276:15736–40.CrossRefPubMedGoogle Scholar
  72. Petit L, Gibert M, Gourch A, Bens M, Vandewalle A, Popoff MR. Clostridium perfringens Epsilon Toxin rapidly decreases membrane barrier permeability of polarized MDCK Cells. Cell Microbiol. 2003;5:155–64.CrossRefPubMedGoogle Scholar
  73. Popoff MR, Bouvet P. Clostridial toxins. Future Microbiol. 2009;4:1021–64.CrossRefPubMedGoogle Scholar
  74. Popoff MR, Bouvet P. Genetic characteristics of toxigenic Clostridia and toxin gene evolution. Toxicon. 2013;75(g):63–89.CrossRefPubMedGoogle Scholar
  75. Robertson SL, Li J, Uzal FA, McClane BA. Evidence for a prepore stage in the action of Clostridium perfringens epsilon toxin. PLoS One. 2011;6(7):e22053.CrossRefPubMedPubMedCentralGoogle Scholar
  76. Rood JI. Virulence genes of Clostridium perfringens. Annu Rev Microbiol. 1998;52:333–60.CrossRefPubMedGoogle Scholar
  77. Rumah KR, Linden J, Fischetti VA, Vartanian T. Isolation of Clostridium perfringens type B in an individual at first clinical presentation of multiple sclerosis provides clues for environmental triggers of the disease. PLoS One. 2013;8(10):e76359.CrossRefPubMedPubMedCentralGoogle Scholar
  78. Rumah KR, Ma Y, Linden JR, Oo ML, Anrather J, Schaeren-Wiemers N, Alonso MA, Fischetti VA, McClain MS, Vartanian T. The myelin and lymphocyte protein MAL is required for binding and activity of Clostridium perfringens epsilon-toxin. PLoS Pathog. 2015;11(5):e1004896.CrossRefPubMedPubMedCentralGoogle Scholar
  79. Sakurai J. Toxins of Clostridium perfringens. Rev Med Microbiol. 1995;6:175–85.Google Scholar
  80. Sayeed S, Li J, McClane BA. Virulence plasmid diversity in Clostridium perfringens type D isolates. Infect Immun. 2007;75(5):2391–8.CrossRefPubMedPubMedCentralGoogle Scholar
  81. Schaeren-Wiemers N, Valenzuela DM, Frank M, Schwab ME. Characterization of a rat gene, rMAL, encoding a protein with four hydrophobic domains in central and peripheral myelin. J Neurosci. 1995;15(8):5753–64.PubMedGoogle Scholar
  82. Schleberger C, Hochmann H, Barth H, Aktories K, Schulz GE. Structure and action of the binary C2 toxin from Clostridium botulinum. J Mol Biol. 2006;364:705–15.CrossRefPubMedGoogle Scholar
  83. Shortt SJ, Titball RW, Lindsay CD. An assessment of the in vitro toxicology of Clostridium perfringens type D epsilon-toxin in human and animal cells. Hum Exp Toxicol. 2000;19(2):108–16.CrossRefPubMedGoogle Scholar
  84. Slemmer JE, De Zeeuw CI, Weber JT. Don’t get too excited: mechanisms of glutamate-mediated Purkinje cell death. Prog Brain Res. 2005;148:367–90.CrossRefPubMedGoogle Scholar
  85. Soler-Jover A, Dorca J, Popoff MR, Gibert M, Saura J, Tusell JM, Serratosa J, Blasi J, Martin-Satue M. Distribution of Clostridium perfringens epsilon toxin in the brains of acutely intoxicated mice and its effect upon glial cells. Toxicon. 2007;50(4):530–40.CrossRefPubMedGoogle Scholar
  86. Sully EK, Whaley K, Bohorova N, Bohorov O, Goodman C, Kim D, Pauly M, Velasco J, Holtsberg FW, Stavale E, Aman MJ, Tangudu C, Uzal FA, Mantis NJ, Zeitlin L. A tripartite cocktail of chimeric monoclonal antibodies passively protects mice against ricin, staphylococcal enterotoxin B and Clostridium perfringens epsilon toxin. Toxicon. 2014;92:36–41.CrossRefPubMedGoogle Scholar
  87. Titball RW. Clostridium perfringens vaccines. Vaccine. 2009;27 Suppl 4:D44–7.CrossRefPubMedGoogle Scholar
  88. Trapp BD, Nave KA. Multiple sclerosis: an immune or neurodegenerative disorder? Annu Rev Neurosci. 2008;31:247–69. doi:10.1146/annurev.neuro.1130.051606.094313.CrossRefPubMedGoogle Scholar
  89. Tsutsui K, Minami J, Matsushita O, Katayama S, Taniguchi Y, Nakamura S, Nishioka M, Okabe A. Phylogenetic analysis of phospholipase C genes from Clostridium perfringens types A to E and Clostridium novyi. J Bacteriol. 1995;177:7164–70.CrossRefPubMedPubMedCentralGoogle Scholar
  90. Turkcan S, Masson JB, Casanova D, Mialon G, Gacoin T, Boilot JP, Popoff MR, Alexandrou A. Observing the confinement potential of bacterial pore-forming toxin receptors inside rafts with nonblinking eu(3+)-doped oxide nanoparticles. Biophys J. 2012;102(10):2299–308.Google Scholar
  91. Turkcan S, Richly MU, Alexandrou A, Masson JB. Probing membrane protein interactions with their lipid raft environment using single-molecule tracking and Bayesian inference analysis. PLoS One. 2013a;8(1):e53073. doi: 10.1371/journal.pone.0053073.Google Scholar
  92. Turkcan S, Richly MU, Bouzigues CI, Allain JM, Alexandrou A. Receptor displacement in the cell membrane by hydrodynamic force amplification through nanoparticles. Biophys J. 2013b;105(1):116–26. doi:10.1016/j.bpj.2013.05.045.Google Scholar
  93. Tweten RK. Clostridium perfringens beta toxin and Clostridium septicum alpha toxin: their mechanisms and possible role in pathogenesis. Vet Microbiol. 2001;82:1–9.CrossRefPubMedGoogle Scholar
  94. Uzal FA, Kelly WR. Effects of the intravenous administration of Clostridium perfringens type D epsilon toxin on young goats and lambs. J Comp Pathol. 1997;116(1):63–71.CrossRefPubMedGoogle Scholar
  95. Uzal FA, Glastonbury JR, Kelly WR, Thomas R. Caprine enterotoxaemia associated with cerebral microangiopathy. Vet Rec. 1997;141(9):224–6.CrossRefPubMedGoogle Scholar
  96. Uzal FA, Kelly WR, Morris WE, Bermudez J, Baison M. The pathology of peracute experimental Clostridium perfringens type D enterotoxemia in sheep. J Vet Diagn Invest. 2004;16(5):403–11.CrossRefPubMedGoogle Scholar
  97. Wioland L, Dupont JL, Bossu JL, Popoff MR, Poulain B. Attack of the nervous system by Clostridium perfringens Epsilon toxin: from disease to mode of action on neural cells. Toxicon. 2013;75:122–35.CrossRefPubMedGoogle Scholar
  98. Wioland L, Dupont JL, Doussau F, Gaillard S, Heid F, Isope P, Pauillac S, Popoff MR, Bossu JL, Poulain B. Epsilon toxin from Clostridium perfringens acts on oligodendrocytes without forming pores, and causes demyelination. Cell Microbiol. 2015;17(3):369–88.CrossRefPubMedGoogle Scholar
  99. Zhu C, Ghabriel MN, Blumbergs PC, Reilly PL, Manavis J, Youssef J, Hatami S, Finnie JW. Clostridium perfringens prototoxin-induced alteration of endothelial barrier antigen (EBA) immunoreactivity at the blood-brain barrier (BBB). Exp Neurol. 2001;169(1):72–82.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2018

Authors and Affiliations

  1. 1.Institut Pasteur, Bactéries Anaérobies et ToxinesParisFrance
  2. 2.Biology DepartmentWilson CollegeChambersburgUSA
  3. 3.Institut des Neurosciences Cellulaires et Intégratives, UPR3212 CNRS, associé à l’Université de Strasbourg, Centre de NeurochimieStrasbourgFrance

Personalised recommendations

Cite entry