On the interaction of Clostridium perfringens enterotoxin with claudins

Toxins

Volumn 2, Issue 6, 2010, Pages 1336-1356

  Veshnyakova, Anna ^a   Protze, Jonas ^a   Rossa, Jan ^a   Blasig, Ingolf E ^a   Krause, Gerd ^a   Piontek, Joerg ^a  

^a LEIBNIZ INSTITUT FÜR MOLEKULARE PHARMAKOLOGIE   (Germany)

Author keywords

Claudins; Clostridium perfringens enterotoxin; Drug delivery; Tight junction

Indexed keywords

CLAUDIN 1; CLAUDIN 2; CLAUDIN 3; CLAUDIN 4; CLOSTRIDIUM PERFRINGENS ENTEROTOXIN; ENTEROTOXIN; PEPTIDOMIMETIC AGENT; RECOMBINANT PROTEIN; UNCLASSIFIED DRUG;

AMINO TERMINAL SEQUENCE; BINDING ASSAY; BRAIN CANCER; BRAIN METASTASIS; CARBOXY TERMINAL SEQUENCE; CELL MEMBRANE; CHANNEL GATING; CLOSTRIDIUM PERFRINGENS; CYTOTOXICITY; DRUG DELIVERY SYSTEM; HOST CELL; HUMAN; IN VITRO STUDY; MAMMAL CELL; MUTAGENESIS; NONHUMAN; PROTEIN EXPRESSION; PROTEIN INTERACTION; RECEPTOR AFFINITY; REVIEW; TIGHT JUNCTION; TUMOR;

ANIMALS; BACTERIAL TOXINS; CLAUDINS; CLOSTRIDIUM PERFRINGENS; ENTEROTOXINS; HUMANS; RECOMBINANT PROTEINS;

CLOSTRIDIUM PERFRINGENS; MAMMALIA;

EID: 79952079601     PISSN: None     EISSN: 20726651     Source Type: Journal    
DOI: 10.3390/toxins2061336     Document Type: Review

References (86)

1. McClane, B.A. The complex interactions between Clostridium perfringens enterotoxin and epithelial tight junctions. Toxicon 2001, 39, 1781-1791.
2. Smedley, J.G., III; McClane, B.A. Fine mapping of the N-terminal cytotoxicity region of Clostridium perfringens enterotoxin by site-directed mutagenesis. Infect. Immun. 2004, 72, 6914-6923.
3. Miyakawa, M.E.F.; Creydt, V.P.; Uzal, F.A.; McClane, B.A.; Ibarra, C. Clostridium perfringens enterotoxin damages the human intestine in vitro. Infect. Immun. 2005, 73, 8407-8410.
4. Sonoda, N.; Furuse, M.; Sasaki, H.; Yonemura, S.; Katahira, J.; Horiguchi, Y.; Tsukita, S. Clostridium perfringens enterotoxin fragment removes specific claudins from tight junction strands: Evidence for direct involvement of claudins in tight junction barrier. J. Cell Biol. 1999, 147, 195-204.
5. Kondoh, M.; Masuyama, A.; Takahashi, A.; Asano, N.; Mizuguchi, H.; Koizumi, N.; Fujii, M.; Hayakawa, T.; Horiguchi, Y.; Watanbe, Y. A novel strategy for the enhancement of drug absorption using a claudin modulator. Mol. Pharmacol. 2005, 67, 749-756.
6. Rood, J.I. Virulence genes of Clostridium perfringens. Annu. Rev. Microbiol. 1998, 52, 333-360.
7. Sakurai, J.; Nagahama, M.; Oda, M. Clostridium perfringens alpha-toxin: Characterization and mode of action. J. Biochem. 2004, 136, 569-574.
8. Awad, M.M.; Ellemor, D.M.; Boyd, R.L.; Emmins, J.J.; Rood, J.I. Synergistic effects of alpha-toxin and perfringolysin O in Clostridium perfringens-mediated gas gangrene. Infect. Immun. 2001, 69, 7904-7910.
9. Nagahama, M.; Hayashi, S.; Morimitsu, S.; Sakurai, J. Biological activities and pore formation of Clostridium perfringens beta toxin in HL 60 cells. J. Biol. Chem. 2003, 278, 36934-36941.
10. Fisher, D.J.; Fernandez-Miyakawa, M.E.; Sayeed, S.; Poon, R.; Adams, V.; Rood, J.I.; Uzal, F.A.; McClane, B.A. Dissecting the contributions of Clostridium perfringens type C toxins to lethality in the mouse intravenous injection model. Infect. Immun. 2006, 74, 5200-5210.
11. 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, 39463-39468.
12. Petit, L.; Gibert, M.; Gourch, A.; Bens, M.; Vandewalle, A.; Popoff, M.R. Clostridium perfringens epsilon toxin rapidly decreases membrane barrier permeability of polarized MDCK cells. Cell. Microbiol. 2003, 5, 155-164.
13. Petit, L.; Maier, E.; Gibert, M.; Popoff, M.R.; 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, 15736-15740.
14. Loffler, A.; Labbe, R.G. Isolation of An Inclusion Body from Sporulating, Enterotoxin-Positive Clostridium-Perfringens. FEMS Microbiol. Lett. 1985, 27, 143-147.
15. Loffler, A.; Labbe, R. Characterization of A Parasporal Inclusion Body from Sporulating, Enterotoxin-Positive Clostridium-Perfringens Type-A. J. Bacteriol. 1986, 165, 542-548.
16. Duncan, C.L.; Sugiyama, H.; Strong, D.H. Rabbit Ileal Loop Response to Strains of Clostridium Perfringens. J. Bacteriol. 1968, 95, 1560-1566.
17. Strong, D.H.; Duncan, C.L.; Perna, G. Clostridium-Perfringens Type-A Food Poisoning. 2. Response of Rabbit Ileum As An Indication of Enteropathogenicity of Strains of Clostridium-Perfringens in Human Beings. Infect. Immun. 1971, 3, 171-178.
18. Niilo, L. Fluid Secretory Response of Bovine Thiry Jejunal Fistula to Enterotoxin of Clostridium-Perfringens. Infect. Immun. 1973, 7, 1-4.
19. Skjelkvale, R.; Uemura, T. Experimental Diarrhea in Human Volunteers Following Oral-Administration of Clostridium-Perfringens Enterotoxin. J. Appl. Bacteriol. 1977, 43, 281-286.
20. Sarker, R.; Carman, R.J.; McClane, B.A. 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. 1999, 33, 946-958.
21. Czeczulin, J.R.; Hanna, P.C.; McClane, B.A. Cloning, Nucleotide Sequencing, and Expression of the Clostridium-Perfringens Enterotoxin Gene in Escherichia-Coli. Infect. Immun. 1993, 61, 3429-3439.
22. Fujinaga, Y.; Inoue, K.; Shimazaki, S.; Tomochika, K.; Tsuzuki, K.; Fujii, N.; Watanabe, T.; Ohyama, T.; Takeshi, K.; Inoue, K.; Oguma, K. Molecular Construction of Clostridium-Botulinum Type-C Progenitor Toxin and Its Gene Organization. Biochem. Biophys. Res. Commun. 1994, 205, 1291-1298.
23. Sherman, S.; Klein, E.; McClane, B.A. Clostridium-Perfringens Type-A Enterotoxin Induces Tissue-Damage and Fluid Accumulation in Rabbit Ileum. J. Diarrhoeal Dis. Res. 1994, 12, 200-207.
24. McDonel, J.L.; Chang, L.W.; Pounds, J.G.; Duncan, C.L. Effects of Clostridium-Perfringens Enterotoxin on Rat and Rabbit Ileum - Electron-Microscopic Study. Lab. Invest. 1978, 39, 210-218.
25. Singh, U.; Mitic, L.L.; Wieckowski, E.U.; Anderson, J.M.; McClane, B.A. 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. 2001, 276, 33402-33412.
26. Matsuda, M.; Sugimoto, N. Calcium-Independent and Dependent Steps in Action of Clostridium-Perfringens Enterotoxin on Hela and Vero Cells. Biochem. Biophys. Res. Commun. 1979, 91, 629-636.
27. McClane, B.A.; McDonel, J.L. The effects of Clostridium perfringens enterotoxin on morphology, viability, and macromolecular synthesis in Vero cells. J. Cell Physiol. 1979, 99, 191-200.
28. Katahira, J., Sugiyama, H.; Inoue, N.; Horiguchi, Y.; Matsuda, M.; Sugimoto, N. Clostridium perfringens enterotoxin utilizes two structurally related membrane proteins as functional receptors in vivo. J. Biol. Chem. 1997, 272, 26652-26658.
29. Robertson, S.L.; Smedley, J.G., III.; Singh, U.; Chakrabarti, G.; Van Itallie, C.M.; Anderson, J.M.; McClane, B.A. Compositional and stoichiometric analysis of Clostridium perfringens enterotoxin complexes in Caco-2 cells and claudin 4 fibroblast transfectants. Cell Microbiol. 2007, 9, 2734-2755.
30. Wieckowski, E.U.; Wnek, A.P.; McClane, B.A. Evidence That An Approximate-To-50-Kda Mammalian Plasma-Membrane Protein with Receptor-Like Properties Mediates the Amphiphilicity of Specifically Bound Clostridium-Perfringens Enterotoxin. J. Biol. Chem. 1994, 269, 10838-10848.
31. Wieckowski, E.U.; Kokai-Kun, J.F.; McClane, B.A. Characterization of membrane-associated Clostridium perfringens enterotoxin following pronase treatment. Infect. Immun. 1998, 66, 5897-5905.
32. Smedley, J.G.; Uzal, F.A.; McClane, B.A. Identification of a prepore large-complex stage in the mechanism of action of Clostridium perfringens enterotoxin. Infect. Immun. 2007, 75, 2381-2390.
33. Chakrabarti, G.; McClane, B.A. The importance of calcium influx, calpain and calmodulin for the activation of CaCo-2 cell death pathways by Clostridium perfringens enterotoxin. Cell. Microbiol. 2005, 7, 129-146.
34. Kokai-Kun, J.F.; McClane, B.A. Deletion analysis of the Clostridium perfringens enterotoxin. Infect. Immun. 1997, 65, 1014-1022.
35. Kokai-Kun, J.F.; Benton, K., Wieckowski, E.U., McClane, B.A. Identification of a Clostridium perfringens enterotoxin region required for large complex formation and cytotoxicity by random mutagenesis. Infect. Immun. 1999, 67, 5634-5641.
36. Hanna, P.C.; Mietzner, T.A.; Schoolnik G.K.; McClane, B.A. Localization of the receptor-binding region of Clostridium perfringens enterotoxin utilizing cloned toxin fragments and synthetic peptides. The 30 C-terminal amino acids define a functional binding region. J. Biol. Chem. 1991, 266, 11037-11043.
37. Winkler, L.; Gehring, C.; Wenzel, A.; Muller, S.L.; Piehl, C.; Krause, G.; Blasig, I.E.; Piontek, J. Molecular Determinants of the Interaction between Clostridium perfringens Enterotoxin Fragments and Claudin-3. J. Biol. Chem. 2009, 284, 18863-18872.
38. Van Itallie, C.M.; Betts, L.; Smedley, J.G.; McClane, B.A.; Anderson, J.M. Structure of the claudin-binding domain of Clostridium perfringens enterotoxin. J. Biol. Chem. 2008, 283, 268-274.
39. Wilson, J.J.; Matsushita, O.; Okabe, A.; Sakon, J. A bacterial collagen-binding domain with novel calcium-binding motif controls domain orientation. EMBO J. 2003, 22, 1743-1752.
40. Boonserm, P.; Davis, P.; Ellar, D.J.; Li, J. Crystal structure of the mosquito-iarvicidal toxin Cry4Ba and its biological implications. J. Mol. Biol. 2005, 348, 363-382.
41. Katahira, J.; Inoue, N.; Horiguchi, Y.; Matsuda, M.; Sugimoto, N. Molecular cloning and functional characterization of the receptor for Clostridium perfringens enterotoxin. J. Cell Biol. 1997, 136, 1239-1247.
42. Morita, K.; Furuse, M.; Fujimoto, K.; Tsukita, S. Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. Proc. Natl. Acad. Sci. USA 1999, 96, 511-516.
43. Fujita, K.; Katahira, J.; Horiguchi, Y.; Sonoda, N.; Furuse, M.; Tsukita, S. Clostridium perfringens enterotoxin binds to the second extracellular loop of claudin-3, a tight junction integral membrane protein. FEBS Lett. 2000, 476, 258-261.
44. Kimura, J.; Abe, H.; Kamitani, S.; Toshima, H.; Fukui, A.; Miyake, M.; Kamata, Y.; Sugita-Konishi, Y.; Yamamoto, S., Horiguchi, Y. Clostridium perfringens Enterotoxin Interacts with Claudins via Electrostatic Attraction. J. Biol. Chem. 2010, 285, 401-408.
45. Krause, G.; Winkler, L.; Mueller, S.L.; Haseloff, R.F.; Piontek, J.; Blasig, I.E. Structure and function of claudins. Biochim. Biophys. Acta 2008, 1778, 631-645.
46. Staehelin, L.A. Structure and function of intercellular junctions. Int. Rev. Cytol. 1974, 39, 191-283.
47. Furuse, M.; Hirase, T.; Itoh, M.; Nagafuchi, A.; Yonemura, S.; Tsukita, S.; Tsukita, S. Occludin: a novel integral membrane protein localizing at tight junctions. J. Cell Biol. 1993, 123, 1777-1788.
48. Ikenouchi, J.; Furuse, M.; Furuse, K.; Sasaki, H.; Tsukita, S.; Tsukita, S. Tricellulin constitutes a novel barrier at tricellular contacts of epithelial cells. J. Cell Biol. 2005, 171, 939-945.
49. Steed, E.; Rodrigues, N.T.; Balda, M.S.; Matter, K. Identification of MarvelD3 as a tight junction-associated transmembrane protein of the occludin family. BMC Cell Biol. 2009, 10, 95.
50. Gonzalez-Mariscal, L.; Betanzos, A.; Nava, P.; Jaramillo, B.E. Tight junction proteins. Prog. Biophys. Mol. Biol. 2003, 81, 1-44.
51. Umeda, K.; Ikenouchi, J.; Katahira-Tayama, S.; Furuse, K.; Sasaki, H.; Nakayama, M.; Matsui, T.; Tsukita, S.; Furuse, M.; Tsukita, S. ZO-1 and ZO-2 independently determine where claudins are polymerized in tight-junction strand formation. Cell 2006, 126, 741-754.
52. Yu, A.S.; Cheng, M.H.; Angelow, S.; Gunzel, D.; Kanzawa, S.A.; Schneeberger, E.E.; Fromm, M.; Coalson, R.D. Molecular basis for cation selectivity in claudin-2-based paracellular pores: identification of an electrostatic interaction site. J. Gen. Physiol. 2009, 133, 111-127.
53. Daugherty, B.L.; Ward, C.; Smith, T.; Ritzenthaler, J.D.; Koval, M. Regulation of heterotypic claudin compatibility. J. Biol. Chem. 2007, 282, 30005-30013.
54. Piontek, J.; Winkler, L.; Wolburg, H.; Muller, S.L.; Zuleger, N.; Piehl, C.; Wiesner, B.; Krause, G.; Blasig, I.E. Formation of tight junction: determinants of homophilic interaction between classic claudins. FASEB J. 2008, 22, 146-158.
55. Zhang, J.; Piontek, J.; Wolburg, H.; Piehl, C.; Liss, M.; Otten, C.; Christ, A.; Willnow, T.E.; Blasig, I.E.; Abdelilah-Seyfried, S. Establishment of a neuroepithelial barrier by Claudin5a is essential for zebrafish brain ventricular lumen expansion. Proc. Natl. Acad. Sci. USA 2010, 107, 1425-1430.
56. Piehl, C.; Piontek, J.; Cording, J.; Wolburg, H.; Blasig, I.E. Participation of the second extracellular loop of claudin-5 in paracellular tightening against ions, small and large molecules. Cell Mol. Life Sci. 2010, doi:10.1007/s00018-010-0332-8.
57. Krause, G.; Winkler, L.; Piehl, C.; Blasig, I.; Piontek, J.; Muller, S.L. Structure and Function of Extracellular Claudin Domains. Ann. N.Y. Acad. Sci. 2009, 1165, 34-43.
58. Ling, J.; Liao, H.; Clark, R.; Wong, M.S.; Lo, D.D. Structural constraints for the binding of short peptides to claudin-4 revealed by surface plasmon resonance. J. Biol. Chem. 2008, 283, 30585-30595.
59. Harada, M.; Kondoh, M.; Ebihara, C.; Takahashi, A.; Komiya, E.; Fujii, M.; Mizuguchi, H.; Tsunoda, S.; Horiguchi, Y.; Yagi, K.; Watanabe, Y. Role of tyrosine residues in modulation of claudin-4 by the C-terminal fragment of Clostridium perfringens enterotoxin. Biochem. Pharmacol. 2007, 73, 206-214.
60. Takahashi, A.; Komiya, E.; Kakutani, H.; Yoshida, T.; Fujii, M.; Horiguchi, Y.; Mizuquchi, H.; Tsutsumi, Y.; Tsunoda, S.I.; Koizumi, N.; Isoda, K.; Yagi, K.; Watanabe, Y.; Kondoh, M. Domain mapping of a claudin-4 modulator, the C-terminal region of C-terminal fragment of Clostridium perfringens enterotoxin, by site-directed mutagenesis. Biochem. Pharmacol. 2008, 75, 1639-1648.
61. Lohrberg, D.; Krause, E.; Schumann, M.; Piontek, J.; Winkler, L.; Blasig, I.E.; Haseloff, R.F. A strategy for enrichment of claudins based on their affinity to Clostridium perfringens enterotoxin. BMC Cell Biol. 2009, 10, 61.
62. Robertson, S.L.; Smedley, J.G.; McClane, B.A. Identification of a Claudin-4 Residue Important for Mediating the Host Cell Binding and Action of Clostridium perfringens Enterotoxin. Infect. Immun. 2010, 78, 505-517.
63. Ebihara, C.; Kondoh, M.; Hasuike, N.; Harada, M.; Mizuguchi, H.; Horiguchi, Y.; Fujii, M.; Watanabe, Y. Preparation of a claudin-targeting molecule using a C-terminal fragment of Clostridium perfringens enterotoxin. J. Pharmacol. Exp. Ther. 2006, 316, 255-260.
64. Swisshelm K,.; Machl, A.; Planitzer, S.; Robertson, R.; Kubbies, M.; Hosier, S. SEMP1, a senescence-associated cDNA isolated from human mammary epithelial cells, is a member of an epithelial membrane protein superfamily. Gene 1999, 226, 285-295.
65. Uchida, H.; Kondoh, M.; Hanada, T.; Takahashi, A.; Hamakubo, T.; Yagi, K. A claudin-4 modulator enhances the mucosal absorption of a biologically active peptide. Biochem. Pharmacol. 2010, 79, 1437-1444.
66. Ebihara, C.; Kondoh, M.; Harada, M.; Fujii, M.; Mizuguchi, H.; Tsunoda, S.; Horiguchi, Y.; Yagi, K.; Watanabe, Y. Role of Tyr306 in the C-terminal fragment of Clostridium perfringens enterotoxin for modulation of tight junction. Biochem. Pharmacol. 2007, 73, 824-830.
67. Takahashi, A.; Kondoh, M.; Masuyama, A.; Fujii, M.; Mizuguchi, H.; Horiguchi, Y.; Watanabe, Y. Role of C-terminal regions of the C-terminal fragment of Clostridium perfringens enterotoxin in its interaction with claudin-4. J. Control. Release 2005, 108, 56-62.
68. Mizuno, N.; Niwa, T.; Yotsumoto, Y.; Sugiyama, Y. Impact of drug transporter studies on drug discovery and development. Pharmacol. Rev. 2003, 55, 425-461.
69. Aungst, B.J. Intestinal permeation enhancers. J. Pharm. Sci. 2000, 89, 429-442.
70. Salama, N.N.; Eddington, N.D.; Fasano, A. Tight junction modulation and its relationship to drug delivery. Adv. Drug Delivery Rev. 2006, 58, 15-28.
71. Hochman, J.; Artursson, P. Mechanisms of Absorption Enhancement and Tight Junction Regulation. J. Controlled Release 1994, 29, 253-267.
72. Yamamoto, A.; Uchiyama, T.; Nishikawa, R.; Fujita, T.; Muranishi, S. Effectiveness and toxicity screening of various absorption enhancers in the rat small intestine: Effects of absorption enhancers on the intestinal absorption of phenol red and the release of protein and phospholipids from the intestinal membrane. J. Pharm. Pharmacol. 1996, 48, 1285-1289.
73. Kondoh, M.; Takahashi, A.; Fujii, M.; Yagi, K.; Watanabe, Y. A novel strategy for a drug delivery system using a claudin modulator. Biol. Pharm. Bull. 2006, 29, 1783-1789.
74. Furuse, M.; Hata, M.; Furuse, K.; Yoshida, Y.; Haratake, A.; Sugitani, Y.; Noda, T.; Kubo, A.; Tsukita, S. Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice. J. Cell Biol. 2002, 156, 1099-1111.
75. Nitta, T.; Hata, M.; Gotoh, S.; Seo, Y.; Sasaki, H.; Hashimoto, N.; Furuse, M.; Tsukita, S. Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J. Cell Biol. 2003, 161, 653-660.
76. Kominsky, S.L.; Tyler, B.; Sosnowski, J.; Brady K.; Doucet, M.; Nell, D.; Smedley, J.G., III; McClane, B.; Brem, H.; Sukumar, S. Clostridium perfringens enterotoxin as a novel-targeted therapeutic for brain metastasis. Cancer Res. 2007, 67, 7977-7982.
77. Santin, A.D.; Bellone, S.; Marizzoni, M.; Palmieri, M.; Siegel, E.R.; McKenney, J.K.; Hennings, L.; Comper, F.; Bandiera, E.; Pecorelli, S. Overexpression of claudin-3 and claudin-4 receptors in uterine serous papillary carcinoma - Novel targets for a type-specific therapy using Clostridium perfringens enterotoxin (CPE). Cancer 2007, 109, 1312-1322.
78. Morin, P.J. Claudin proteins in ovarian cancer. Dis. Markers 2007, 23, 453-457.
79. Morin, P.J. Claudin proteins in human cancer: Promising new targets for diagnosis and therapy. Cancer Res. 2005, 65, 9603-9606.
80. Potala, S.; Sahoo, S.K.; Verma, R.S. Targeted therapy of cancer using diphtheria toxin-derived immunotoxins. Drug Discov. Today 2008, 13, 807-815.
81. Kreitman, R.J.; Pastan, I. Immunotoxins in the treatment of refractory hairy cell leukemia. Hematol. Oncol. Clin. N. Am. 2006, 20, 1137-1151.
82. Kakutani, H.; Kondoh, M.; Saeki, R.; Fujii, M.; Watanabe, Y.; Mizuguchi, H.; Yagi, K. Claudin-4-targeting of diphtheria toxin fragment A using a C-terminal fragment of Clostridium perfringens enterotoxin. Eur. J. Pharm. Biopharm. 2010, 75, 213-217.
83. Yuan, X.Q.; Lin, X.J.; Manorek, G.; Kanatani, I.; Cheung, L.H.; Rosenblum, M.G.; Howell, S.B. Recombinant CPE fused to tumor necrosis factor targets human ovarian cancer cells expressing the claudin-3 and claudin-4 receptors. Mol. Cancer Ther. 2009, 8, 1906-1915.
84. Michl, P.; Buchholz, M.; Rolke, M.; Kunsch, S.; Lohr, M.; McClane, B.; Tsukita, S.; Leder, G.; Adler, G.; Gress, T.M. Claudin-4: A new target for pancreatic cancer treatment using Clostridium perfringens enterotoxin. Gastroenterology 2001, 121, 678-684.
85. Santin, A.D.; Cane, S.; Bellone, S.; Palmieri, M.; Siegel, E.R.; Thomas, M.; Roman, J.J.; Burnett, A.; Cannon, M.J.; Pecorelli, S. Treatment of chemotherapy-resistant human ovarian cancer xenografts in C.B-17/SCID mice by intraperitoneal administration of Clostridium perfringens enterotoxin. Cancer Res. 2005, 65, 4334-4342.
86. Meertens, L.; Bertaux, C.; Cukierman, L.; Cormier, E.; Lavillette, D.; Cosset, F.L.; Dragic, T. The tight junction proteins claudin-1, -6, and -9 are entry cofactors for hepatitis C virus. J. Virol. 2008, 82, 3555-3560.