The Myelin and Lymphocyte Protein MAL Is Required for Binding and Activity of ε-Toxin
Clostridium perfringens epsilon-toxin is a potent pore-forming toxin responsible for a devastating central nervous system disease in livestock and has been suggested as a possible environmental trigger for Multiple Sclerosis. Epsilon-toxin binds with great specificity to a restricted number of host cell types and structures, for example gut epithelial cells, blood-brain barrier endothelial cells, and myelin. While most pore-forming toxins achieve binding through specific interaction with respective receptors on the cell membrane, the receptor for epsilon-toxin, however, is unknown. In this report we identify the Myelin and Lymphocyte protein, MAL, as being necessary for binding and cytotoxic effects of epsilon-toxin, and we show its second extracellular loop is critical in this novel function. At a physiological level, mice homozygous for a targeted deletion of the MAL gene lack sensitivity to epsilon-toxin whereas the toxin is lethal in wild-type mice. These observations lead to the possibility that MAL is a candidate receptor for epsilon-toxin. However, we have not demonstrated a physical interaction between epsilon-toxin and MAL.
Vyšlo v časopise:
The Myelin and Lymphocyte Protein MAL Is Required for Binding and Activity of ε-Toxin. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004896
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004896
Souhrn
Clostridium perfringens epsilon-toxin is a potent pore-forming toxin responsible for a devastating central nervous system disease in livestock and has been suggested as a possible environmental trigger for Multiple Sclerosis. Epsilon-toxin binds with great specificity to a restricted number of host cell types and structures, for example gut epithelial cells, blood-brain barrier endothelial cells, and myelin. While most pore-forming toxins achieve binding through specific interaction with respective receptors on the cell membrane, the receptor for epsilon-toxin, however, is unknown. In this report we identify the Myelin and Lymphocyte protein, MAL, as being necessary for binding and cytotoxic effects of epsilon-toxin, and we show its second extracellular loop is critical in this novel function. At a physiological level, mice homozygous for a targeted deletion of the MAL gene lack sensitivity to epsilon-toxin whereas the toxin is lethal in wild-type mice. These observations lead to the possibility that MAL is a candidate receptor for epsilon-toxin. However, we have not demonstrated a physical interaction between epsilon-toxin and MAL.
Zdroje
1. Hatheway CL. Toxigenic clostridia. Clin Microbiol Rev. 1990;3(1):66–98. Epub 1990/01/01. 2404569
2. Popoff MR. Epsilon toxin: a fascinating pore-forming toxin. FEBS J. 2011;278(23):4602–15. doi: 10.1111/j.1742-4658.2011.08145.x 21535407
3. Alves GG, Machado de Avila RA, Chavez-Olortegui CD, Lobato FC. Clostridium perfringens epsilon toxin: The third most potent bacterial toxin known. Anaerobe. 2014;30C:102–7.
4. Blackwell TE, Butler DG, Bell JA. Enterotoxemia in the goat: the humoral response and local tissue reaction following vaccination with two different bacterin-toxoids. Can J Comp Med. 1983;47(2):127–32. 6309346
5. Finnie JW. Neurological disorders produced by Clostridium perfringens type D epsilon toxin. Anaerobe. 2004;10(2):145–50. 16701511
6. 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. 15460322
7. Uzal FA, Songer JG. Diagnosis of Clostridium perfringens intestinal infections in sheep and goats. J Vet Diagn Invest. 2008;20(3):253–65. 18460610
8. Gkiourtzidis K, Frey J, Bourtzi-Hatzopoulou E, Iliadis N, Sarris K. PCR detection and prevalence of alpha-, beta-, beta 2-, epsilon-, iota- and enterotoxin genes in Clostridium perfringens isolated from lambs with clostridial dysentery. Vet Microbiol. 2001;82(1):39–43. 11423193
9. Goncalves LA, Lobato ZI, Silva RO, Salvarani FM, Pires PS, Assis RA, et al. Selection of a Clostridium perfringens type D epsilon toxin producer via dot-blot test. Arch Microbiol. 2009;191(11):847–51. doi: 10.1007/s00203-009-0510-y 19779698
10. Uzal FA, Kelly WR, Thomas R, Hornitzky M, Galea F. Comparison of four techniques for the detection of Clostridium perfringens type D epsilon toxin in intestinal contents and other body fluids of sheep and goats. J Vet Diagn Invest. 2003;15(2):94–9. 12661718
11. Bhown AS, Habeerb AF. Structural studies on epsilon-prototoxin of Clostridium perfringens type D. Localization of the site of tryptic scission necessary for activation to epsilon-toxin. Biochem Biophys Res Commun. 1977;78(3):889–96. 199192
12. Freedman JC, Li J, Uzal FA, McClane BA. Proteolytic Processing and Activation of Clostridium perfringens Epsilon Toxin by Caprine Small Intestinal Contents. MBio. 2014;5(5).
13. Habeeb AF, Lee CL, Atassi MZ. Conformational studies on modified proteins and peptides. VII. Conformation of epsilon-prototoxin and epsilon-toxin from Clostridium perfringens. Conformational changes associated with toxicity. Biochim Biophys Acta. 1973;322(2):245–50. 4358084
14. 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(7):527–35. 9272698
15. Worthington RW, Mulders MS. Physical changes in the epsilon prototoxin molecule of Clostridium perfringens during enzymatic activation. Infect Immun. 1977;18(2):549–51. 200566
16. Harkness JM, Li J, McClane BA. Identification of a lambda toxin-negative Clostridium perfringens strain that processes and activates epsilon prototoxin intracellularly. Anaerobe. 2012;18(5):546–52. Epub 2012/09/18. doi: 10.1016/j.anaerobe.2012.09.001 22982043
17. Adamson RH, Ly JC, Fernandez-Miyakawa M, Ochi S, Sakurai J, Uzal F, et al. Clostridium perfringens epsilon-toxin increases permeability of single perfused microvessels of rat mesentery. Infect Immun. 2005;73(8):4879–87. 16041001
18. Tamai E, Ishida T, Miyata S, Matsushita O, Suda H, Kobayashi S, et al. Accumulation of Clostridium perfringens epsilon-toxin in the mouse kidney and its possible biological significance. Infect Immun. 2003;71(9):5371–5. 12933886
19. Finnie JW. Ultrastructural changes in the brain of mice given Clostridium perfringens type D epsilon toxin. J Comp Pathol. 1984;94(3):445–52. 6088599
20. Finnie JW. Pathogenesis of brain damage produced in sheep by Clostridium perfringens type D epsilon toxin: a review. Aust Vet J. 2003;81(4):219–21. 15080445
21. Finnie JW, Manavis J, Casson RJ, Chidlow G. Retinal microvascular damage and vasogenic edema produced by Clostridium perfringens type D epsilon toxin in rats. J Vet Diagn Invest. 2014;26(3):470–2. 24741023
22. Finnie JW, Manavis J, Chidlow G. Loss of endothelial barrier antigen immunoreactivity as a marker of Clostridium perfringens type D epsilon toxin-induced microvascular damage in rat brain. J Comp Pathol. 2014;151(2–3):153–6. doi: 10.1016/j.jcpa.2014.07.002 25172052
23. Soler-Jover A, Dorca J, Popoff MR, Gibert M, Saura J, Tusell JM, et al. 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. 17572464
24. Worthington RW, Mulders MS. Effect of Clostridium perfringens epsilon toxin on the blood brain barrier of mice. Onderstepoort J Vet Res. 1975;42(1):25–7. 171606
25. Zhu C, Ghabriel MN, Blumbergs PC, Reilly PL, Manavis J, Youssef J, et al. Clostridium perfringens prototoxin-induced alteration of endothelial barrier antigen (EBA) immunoreactivity at the blood-brain barrier (BBB). Exp Neurol. 2001;169(1):72–82. 11312560
26. 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. 9076601
27. 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. 10208737
28. Lonchamp E, Dupont JL, Wioland L, Courjaret R, Mbebi-Liegeois C, Jover E, et al. Clostridium perfringens epsilon toxin targets granule cells in the mouse cerebellum and stimulates glutamate release. PLoS One. 2010;5(9).
29. 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. doi: 10.1016/j.toxicon.2013.04.003 23632158
30. Garcia JP, Giannitti F, Finnie JW, Manavis J, Beingesser J, Adams V, et al. Comparative Neuropathology of Ovine Enterotoxemia Produced by Clostridium perfringens Type D Wild-Type Strain CN1020 and Its Genetically Modified Derivatives. Vet Pathol. 2015;52(3):465–75. doi: 10.1177/0300985814540543 24964921
31. Murrell TG, O'Donoghue PJ, Ellis T. A review of the sheep-multiple sclerosis connection. Med Hypotheses. 1986;19(1):27–39. 2871478
32. 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. doi: 10.1371/journal.pone.0076359 24146858
33. 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. 16388606
34. Nagahama M, Itohayashi Y, Hara H, Higashihara M, Fukatani Y, Takagishi T, et al. Cellular vacuolation induced by Clostridium perfringens epsilon-toxin. FEBS J. 2011;278(18):3395–407. doi: 10.1111/j.1742-4658.2011.08263.x 21781280
35. Turkcan S, Alexandrou A, Masson JB. A Bayesian inference scheme to extract diffusivity and potential fields from confined single-molecule trajectories. Biophys J. 2012;102(10):2288–98. doi: 10.1016/j.bpj.2012.01.063 22677382
36. Turkcan S, Masson JB, Casanova D, Mialon G, Gacoin T, Boilot JP, et al. 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. doi: 10.1016/j.bpj.2012.03.072 22677383
37. 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. doi: 10.1371/journal.pone.0017787 21412435
38. Soler-Jover A, Blasi J, Gomez de Aranda I, Navarro P, Gibert M, Popoff MR, et al. Effect of epsilon toxin-GFP on MDCK cells and renal tubules in vivo. J Histochem Cytochem. 2004;52(7):931–42. 15208360
39. 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.
40. Finnie JW. Histopathological changes in the brain of mice given Clostridium perfringens type D epsilon toxin. J Comp Pathol. 1984;94(3):363–70. 6088597
41. Alonso MA, Weissman SM. cDNA cloning and sequence of MAL, a hydrophobic protein associated with human T-cell differentiation. Proc Natl Acad Sci U S A. 1987;84(7):1997–2001. 3494249
42. 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. 7643216
43. Kitadokoro K, Nishimura K, Kamitani S, Fukui-Miyazaki A, Toshima H, Abe H, et al. Crystal structure of Clostridium perfringens enterotoxin displays features of beta-pore-forming toxins. J Biol Chem. 2011;286(22):19549–55. doi: 10.1074/jbc.M111.228478 21489981
44. Ivie SE, McClain MS. Identification of amino acids important for binding of Clostridium perfringens epsilon toxin to host cells and to HAVCR1. Biochemistry. 2012;51(38):7588–95. doi: 10.1021/bi300690a 22938730
45. 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. doi: 10.1016/j.bbamem.2009.09.020 19835840
46. Miyata S, Matsushita O, Minami J, Katayama S, Shimamoto S, Okabe A. Cleavage of a C-terminal peptide is essential for heptamerization of Clostridium perfringens epsilon-toxin in the synaptosomal membrane. J Biol Chem. 2001;276(17):13778–83. 11278924
47. 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. doi: 10.1371/journal.pone.0022053 21814565
48. Miyata S, Minami J, Tamai E, Matsushita O, Shimamoto S, Okabe A. Clostridium perfringens epsilon-toxin forms a heptameric pore within the detergent-insoluble microdomains of Madin-Darby canine kidney cells and rat synaptosomes. J Biol Chem. 2002;277(42):39463–8. 12177068
49. Zacchetti D, Peranen J, Murata M, Fiedler K, Simons K. VIP17/MAL, a proteolipid in apical transport vesicles. FEBS Lett. 1995;377(3):465–9. 8549777
50. Kim T, Fiedler K, Madison DL, Krueger WH, Pfeiffer SE. Cloning and characterization of MVP17: a developmentally regulated myelin protein in oligodendrocytes. J Neurosci Res. 1995;42(3):413–22. 8583510
51. Schaeren-Wiemers N, Schaefer C, Valenzuela DM, Yancopoulos GD, Schwab ME. Identification of new oligodendrocyte- and myelin-specific genes by a differential screening approach. J Neurochem. 1995;65(1):10–22. 7790852
52. Millan J, Puertollano R, Fan L, Rancano C, Alonso MA. The MAL proteolipid is a component of the detergent-insoluble membrane subdomains of human T-lymphocytes. Biochem J. 1997;321 (Pt 1):247–52.
53. Anton O, Batista A, Millan J, Andres-Delgado L, Puertollano R, Correas I, et al. An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytes. J Exp Med. 2008;205(13):3201–13. doi: 10.1084/jem.20080552 19064697
54. Anton OM, Andres-Delgado L, Reglero-Real N, Batista A, Alonso MA. MAL protein controls protein sorting at the supramolecular activation cluster of human T lymphocytes. J Immunol. 2011;186(11):6345–56. doi: 10.4049/jimmunol.1003771 21508261
55. Schaeren-Wiemers N, Bonnet A, Erb M, Erne B, Bartsch U, Kern F, et al. The raft-associated protein MAL is required for maintenance of proper axon—glia interactions in the central nervous system. J Cell Biol. 2004;166(5):731–42. 15337780
56. Puertollano R, Alonso MA. MAL, an integral element of the apical sorting machinery, is an itinerant protein that cycles between the trans-Golgi network and the plasma membrane. Mol Biol Cell. 1999;10(10):3435–47. 10512878
57. Zhou G, Liang FX, Romih R, Wang Z, Liao Y, Ghiso J, et al. MAL facilitates the incorporation of exocytic uroplakin-delivering vesicles into the apical membrane of urothelial umbrella cells. Mol Biol Cell. 2012;23(7):1354–66. doi: 10.1091/mbc.E11-09-0823 22323295
58. Caduff J, Sansano S, Bonnet A, Suter U, Schaeren-Wiemers N. Characterization of GFP-MAL expression and incorporation in rafts. Microsc Res Tech. 2001;52(6):645–55. 11276117
59. Erne B, Sansano S, Frank M, Schaeren-Wiemers N. Rafts in adult peripheral nerve myelin contain major structural myelin proteins and myelin and lymphocyte protein (MAL) and CD59 as specific markers. J Neurochem. 2002;82(3):550–62. 12153479
60. Magal LG, Yaffe Y, Shepshelovich J, Aranda JF, de Marco Mdel C, Gaus K, et al. Clustering and lateral concentration of raft lipids by the MAL protein. Mol Biol Cell. 2009;20(16):3751–62. doi: 10.1091/mbc.E09-02-0142 19553470
61. Martin-Belmonte F, Arvan P, Alonso MA. MAL mediates apical transport of secretory proteins in polarized epithelial Madin-Darby canine kidney cells. J Biol Chem. 2001;276(52):49337–42. 11673461
62. Martin-Belmonte F, Puertollano R, Millan J, Alonso MA. The MAL proteolipid is necessary for the overall apical delivery of membrane proteins in the polarized epithelial Madin-Darby canine kidney and fischer rat thyroid cell lines. Mol Biol Cell. 2000;11(6):2033–45. 10848627
63. Puertollano R, Martinez-Menarguez JA, Batista A, Ballesta J, Alonso MA. An intact dilysine-like motif in the carboxyl terminus of MAL is required for normal apical transport of the influenza virus hemagglutinin cargo protein in epithelial Madin-Darby canine kidney cells. Mol Biol Cell. 2001;12(6):1869–83. 11408592
64. Ramnarayanan SP, Tuma PL. MAL, but not MAL2, expression promotes the formation of cholesterol-dependent membrane domains that recruit apical proteins. Biochem J. 2011;439(3):497–504. doi: 10.1042/BJ20110803 21732912
65. Lall N, Henley-Smith CJ, De Canha MN, Oosthuizen CB, Berrington D. Viability Reagent, PrestoBlue, in Comparison with Other Available Reagents, Utilized in Cytotoxicity and Antimicrobial Assays. Int J Microbiol. 2013;2013:420601. doi: 10.1155/2013/420601 23653650
66. 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. 20721308
67. Riss TL, Moravec RA, Niles AL, Benink HA, Worzella TJ, Minor L. Cell Viability Assays. In: Sittampalam GS, Gal-Edd N, Arkin M, Auld D, Austin C, Bejcek B, et al., editors. Assay Guidance Manual. Bethesda (MD)2004.
68. 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(3):155–64. 12614459
69. Petit L, Maier E, Gibert M, Popoff MR, Benz R. Clostridium perfringens epsilon toxin induces a rapid change of cell membrane permeability to ions and forms channels in artificial lipid bilayers. J Biol Chem. 2001;276(19):15736–40. 11278669
70. Bowman AM, Nesin OM, Pakhomova ON, Pakhomov AG. Analysis of plasma membrane integrity by fluorescent detection of Tl(+) uptake. J Membr Biol. 2010;236(1):15–26. Epub 2010/07/14. doi: 10.1007/s00232-010-9269-y 20623351
71. 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. Epub 2010/08/05. doi: 10.1016/j.bpj.2010.05.014 20682255
72. Pelish TM, McClain MS. Dominant-negative inhibitors of the Clostridium perfringens epsilon-toxin. J Biol Chem. 2009;284(43):29446–53. doi: 10.1074/jbc.M109.021782 19720828
73. 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(20):6480–7. 9335299
74. Chassin C, Bens M, de Barry J, Courjaret R, Bossu JL, Cluzeaud F, et al. 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. 17567938
75. Bokori-Brown M, Hall CA, Vance C, Fernandes da Costa SP, Savva CG, Naylor CE, et al. Clostridium perfringens epsilon toxin mutant Y30A-Y196A as a recombinant vaccine candidate against enterotoxemia. Vaccine. 2014;32(23):2682–7. doi: 10.1016/j.vaccine.2014.03.079 24709588
76. Bokori-Brown M, Kokkinidou MC, Savva CG, Fernandes da Costa S, Naylor CE, Cole AR, et al. Clostridium perfringens epsilon toxin H149A mutant as a platform for receptor binding studies. Protein Sci. 2013;22(5):650–9. doi: 10.1002/pro.2250 23504825
77. Magyar JP, Ebensperger C, Schaeren-Wiemers N, Suter U. Myelin and lymphocyte protein (MAL/MVP17/VIP17) and plasmolipin are members of an extended gene family. Gene. 1997;189(2):269–75. 9168137
78. Bokori-Brown M, Savva CG, Fernandes da Costa SP, Naylor CE, Basak AK, Titball RW. Molecular basis of toxicity of Clostridium perfringens epsilon toxin. FEBS J. 2011;278(23):4589–601. doi: 10.1111/j.1742-4658.2011.08140.x 21518257
79. Cooper MA. Advances in membrane receptor screening and analysis. J Mol Recognit. 2004;17(4):286–315. Epub 2004/07/01. 15227637
80. Puertollano R, Alonso MA. Targeting of MAL, a putative element of the apical sorting machinery, to glycolipid-enriched membranes requires a pre-golgi sorting event. Biochem Biophys Res Commun. 1999;254(3):689–92. 9920802
81. Marazuela M, Acevedo A, Adrados M, Garcia-Lopez MA, Alonso MA. Expression of MAL, an integral protein component of the machinery for raft-mediated pical transport, in human epithelia. J Histochem Cytochem. 2003;51(5):665–74. 12704214
82. Cheong KH, Zacchetti D, Schneeberger EE, Simons K. VIP17/MAL, a lipid raft-associated protein, is involved in apical transport in MDCK cells. Proc Natl Acad Sci U S A. 1999;96(11):6241–8. 10339572
83. Puertollano R, Martin-Belmonte F, Millan J, de Marco MC, Albar JP, Kremer L, et al. The MAL proteolipid is necessary for normal apical transport and accurate sorting of the influenza virus hemagglutinin in Madin-Darby canine kidney cells. J Cell Biol. 1999;145(1):141–51. 10189374
84. Alonso MA, Millan J. The role of lipid rafts in signalling and membrane trafficking in T lymphocytes. J Cell Sci. 2001;114(Pt 22):3957–65. 11739628
85. Fennessey CM, Sheng J, Rubin DH, McClain MS. Oligomerization of Clostridium perfringens epsilon toxin is dependent upon caveolins 1 and 2. PLoS One. 2012;7(10):e46866. doi: 10.1371/journal.pone.0046866 23056496
86. Batty I, Bullen JJ. The effect of Clostridium welchii type D culture filtrates on the permeability of the mouse intestine. J Pathol Bacteriol. 1956;71(2):311–23. 13398877
87. Chen J, Ma M, Uzal FA, McClane BA. Host cell-induced signaling causes Clostridium perfringens to upregulate production of toxins important for intestinal infections. Gut Microbes. 2014;5(1):96–107. doi: 10.4161/gmic.26419 24061146
88. 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. 12777097
89. Garcia JP, Adams V, Beingesser J, Hughes ML, Poon R, Lyras D, et al. 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. doi: 10.1128/IAI.00238-13 23630957
90. Goldstein J, Morris WE, Loidl CF, Tironi-Farinati C, McClane BA, Uzal FA, et al. Clostridium perfringens epsilon toxin increases the small intestinal permeability in mice and rats. PLoS One. 2009;4(9):e7065. doi: 10.1371/journal.pone.0007065 19763257
91. Layana JE, Fernandez Miyakawa ME, Uzal FA. Evaluation of different fluids for detection of Clostridium perfringens type D epsilon toxin in sheep with experimental enterotoxemia. Anaerobe. 2006;12(4):204–6. 16857397
92. Li J, Sayeed S, Robertson S, Chen J, McClane BA. Sialidases affect the host cell adherence and epsilon toxin-induced cytotoxicity of Clostridium perfringens type D strain CN3718. PLoS Pathog. 2011;7(12):e1002429. doi: 10.1371/journal.ppat.1002429 22174687
93. Martin PK, Naylor RD, Sharpe RT. Detection of Clostridium perfringens beta toxin by enzyme-linked immunosorbent assay. Res Vet Sci. 1988;44(2):270–1. 3387684
94. Miserez R, Frey J, Buogo C, Capaul S, Tontis A, Burnens A, et al. Detection of alpha- and epsilon-toxigenic Clostridium perfringens type D in sheep and goats using a DNA amplification technique (PCR). Lett Appl Microbiol. 1998;26(5):382–6. 9674169
95. Pyakural S, Singh NB. Initial studies on "six months disease" in sheep. Vet Rec. 1976;98(3):49–50. 176766
96. Raibaud P. Experimental models for studying the microbial ecology in the intestinal tract. Acta Gastroenterol Latinoam. 1989;19(4):219–26. 2561802
97. Smedley JG 3rd, Fisher DJ, Sayeed S, Chakrabarti G, McClane BA. The enteric toxins of Clostridium perfringens. Rev Physiol Biochem Pharmacol. 2004;152:183–204. 15517462
98. Uzal FA. Diagnosis of Clostridium perfringens intestinal infections in sheep and goats. Anaerobe. 2004;10(2):135–43. 16701510
99. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402–8. Epub 2002/02/16. 11846609
100. McWilliam H LW, Uludag M, Squizzato S, Park YM, Buso N, Cowley AP, Lopez R. Analysis Tool Web Services from the EMBL-EBI. Nucleic Acids Res 2013 Jul;41(Web Server issue):W597–600. http://www.ebi.ac.uk/Tools/msa/clustalw2/2013. doi: 10.1093/nar/gkt376 23671338
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