Cytotoxicity of Clostridium difficile toxin B does not require cysteine protease-mediated autocleavage and release of the glucosyltransferase domain into the host cell cytosol

Pathogens and Disease

Volumn 67, Issue 1, 2013, Pages 11-18

  Li, Shan ^a,b   Shi, Lianfa ^a   Yang, Zhiyong ^a   Feng, Hanping ^a  

^a UNIVERSITY OF MARYLAND DENTAL SCHOOL   (United States)

^b SOUTH CHINA UNIVERSITY OF TECHNOLOGY   (China)

Author keywords

Autocleavage; Clostridium difficile; Cysteine protease; Cytotoxicity; Toxin B

Indexed keywords

CASPASE 3; CLOSTRIDIUM DIFFICILE TOXIN B; CYSTEINE PROTEINASE; GLUCOSYLTRANSFERASE; MUTANT PROTEIN;

ANIMAL CELL; ARTICLE; CELL SHAPE; CONCENTRATION RESPONSE; CONTROLLED STUDY; CYTOSOL; CYTOTOXICITY; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME RELEASE; GLYCOSYLATION; MOLECULAR MODEL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN DOMAIN; WILD TYPE;

AMINO ACID SUBSTITUTION; ANIMALS; APOPTOSIS; BACTERIAL PROTEINS; BACTERIAL TOXINS; CELL LINE; CLOSTRIDIUM DIFFICILE; CYSTEINE PROTEASES; DNA MUTATIONAL ANALYSIS; EPITHELIAL CELLS; GLUCOSYLTRANSFERASES; MICE; MUTAGENESIS, SITE-DIRECTED; MUTANT PROTEINS; PROTEIN PROCESSING, POST-TRANSLATIONAL;

EID: 84878122416     PISSN: None     EISSN: 2049632X     Source Type: Journal    
DOI: 10.1111/2049-632X.12016     Document Type: Article

References (37)

1. Albesa-Jove D, Bertrand T, Carpenter EP et al. (2010) Four distinct structural domains in Clostridium difficile toxin B visualized using SAXS. J Mol Biol 396: 1260-1270.
2. Barroso LA, Moncrief JS, Lyerly DM & Wilkins TD (1994) Mutagenesis of the Clostridium difficile toxin B gene and effect on cytotoxic activity. Microb Pathog 16: 297-303.
3. Barth H, Pfeifer G, Hofmann F, Maier E, Benz R & Aktories K (2001) Low pH-induced formation of ion channels by Clostridium difficile toxin B in target cells. J Biol Chem 276: 10670-10676.
4. Davies AH, Roberts AK, Shone CC, Acharya KR (2011) Super toxins from a super bug: structure and function of Clostridium difficile toxins. Biochem J 436: 517-526.
5. Egerer M, Giesemann T, Jank T, Satchell KJ & Aktories K (2007) Auto-catalytic cleavage of Clostridium difficile toxins A and B depends on cysteine protease activity. J Biol Chem 282: 25314-25321.
6. Egerer M, Giesemann T, Herrmann C & Aktories K (2009) Autocatalytic processing of Clostridium difficile toxin B. Binding of inositol hexakisphosphate. J Biol Chem 284: 3389-3395.
7. von Eichel-Streiber C, Sauerborn M & Kuramitsu HK (1992) Evidence for a modular structure of the homologous repetitive C-terminal carbohydrate-binding sites of Clostridium difficile toxins and Streptococcus mutans glucosyltransferases. J Bacteriol 174: 6707-6710.
8. Genth H, Huelsenbeck J, Hartmann B, Hofmann F, Just I & Gerhard R (2006) Cellular stability of Rho-GTPases glucosylated by Clostridium difficile toxin B. FEBS Lett 580: 3565-3569.
9. Genth H, Dreger SC, Huelsenbeck J & Just I (2008) Clostridium difficile toxins: more than mere inhibitors of Rho proteins. Int J Biochem Cell Biol 40: 592-597.
10. Giesemann T, Egerer M, Jank T & Aktories K (2008) Processing of Clostridium difficile toxins. J Med Microbiol 57: 690-696.
11. He X, Sun X, Wang J, Wang X, Zhang Q, Tzipori S & Feng H (2009) Antibody-enhanced, Fc gamma receptor-mediated endocytosis of Clostridium difficile toxin A. Infect Immun 77: 2294-2303.
12. Ho JG, Greco A, Rupnik M & Ng KK (2005) Crystal structure of receptor-binding C-terminal repeats from Clostridium difficile toxin A. Proc Natl Acad Sci USA 102: 18373-18378.
13. Hofmann F, Busch C, Prepens U, Just I & Aktories K (1997) Localization of the glucosyltransferase activity of Clostridium difficile toxin B to the N-terminal part of the holotoxin. J Biol Chem 272: 11074-11078.
14. Jank T & Aktories K (2008) Structure and mode of action of clostridial glucosylating toxins: the ABCD model. Trends Microbiol 16: 222-229.
15. Just I, Selzer J, Wilm M, von Eichel-Streiber C, Mann M & Aktories K (1995) Glucosylation of Rho proteins by Clostridium difficile toxin B. Nature 375: 500-503.
16. Kelly CP & LaMont JT (2008) Clostridium difficile-more difficult than ever. N Engl J Med 359: 1932-1940.
17. Kreimeyer I, Euler F, Marckscheffel A et al. (2011) Autoproteolytic cleavage mediates cytotoxicity of Clostridium difficile toxin A. Naunyn Schmiedebergs Arch Pharmacol 383: 253-262.
18. Kuehne SA, Cartman ST, Heap JT, Kelly ML, Cockayne A & Minton NP (2010) The role of toxin A and toxin B in Clostridium difficile infection. Nature 467: 711-713.
19. Lanis JM, Barua S & Ballard JD (2010) Variations in TcdB activity and the hypervirulence of emerging strains of Clostridium difficile. PLoS Pathog 6: e1001061.
20. Lanis JM, Hightower LD, Shen A & Ballard JD (2012) TcdB from hypervirulent Clostridium difficile exhibits increased efficiency of autoprocessing. Mol Microbiol 84: 66-76.
21. Lyras D, O'Connor JR, Howarth PM et al. (2009) Toxin B is essential for virulence of Clostridium difficile. Nature 458: 1176-1179.
22. Nottrott S, Schoentaube J, Genth H, Just I & Gerhard R (2007) Clostridium difficile toxin A-induced apoptosis is p53-independent but depends on glucosylation of Rho GTPases. Apoptosis 12: 1443-1453.
23. Pfeifer G, Schirmer J, Leemhuis J, Busch C, Meyer DK, Aktories K & Barth H (2003) Cellular uptake of Clostridium difficile toxin B. Translocation of the N-terminal catalytic domain into the cytosol of eukaryotic cells. J Biol Chem 278: 44535-44541.
24. Pruitt RN, Chambers MG, Ng KK, Ohi MD & Lacy DB (2010) Structural organization of the functional domains of Clostridium difficile toxins A and B. Proc Natl Acad Sci USA 107: 13467-13472.
25. Qa'Dan M, Spyres LM & Ballard JD (2000) pH-induced conformational changes in Clostridium difficile toxin B. Infect Immun 68: 2470-2474.
26. Qa'Dan M, Ramsey M, Daniel J, Spyres LM, Safiejko-Mroczka B, Ortiz-Leduc W & Ballard JD (2002) Clostridium difficile toxin B activates dual caspase-dependent and caspase-independent apoptosis in intoxicated cells. Cell Microbiol 4: 425-434.
27. Reineke J, Tenzer S, Rupnik M et al. (2007) Autocatalytic cleavage of Clostridium difficile toxin B. Nature 446: 415-419.
28. Rupnik M, Pabst S, Rupnik M, von Eichel-Streiber C, Urlaub H & Soling HD (2005) Characterization of the cleavage site and function of resulting cleavage fragments after limited proteolysis of Clostridium difficile toxin B (TcdB) by host cells. Microbiology 151: 199-208.
29. Rupnik M, Wilcox MH & Gerding DN (2009) Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat Rev Microbiol 7: 526-536.
30. Savidge TC, Urvil P, Oezguen N et al. (2011) Host S-nitrosylation inhibits clostridial small molecule-activated glucosylating toxins. Nat Med 17: 1136-1141.
31. Sheahan KL, Cordero CL & Satchell KJ (2007) Autoprocessing of the Vibrio cholerae RTX toxin by the cysteine protease domain. EMBO J 26: 2552-2561.
32. Shen A, Lupardus PJ, Gersch MM, Puri AW, Albrow VE, Garcia KC & Bogyo M (2011) Defining an allosteric circuit in the cysteine protease domain of Clostridium difficile toxins. Nat Struct Mol Biol 18: 364-371.
33. Stabler RA, Dawson LF, Phua LT & Wren BW (2008) Comparative analysis of BI/NAP1/027 hypervirulent strains reveals novel toxin B-encoding gene (tcdB) sequences. J Med Microbiol 57: 771-775.
34. Voth DE & Ballard JD (2005) Clostridium difficile toxins: mechanism of action and role in disease. Clin Microbiol Rev 18: 247-263.
35. Wang H, Sun X, Zhang Y et al. (2012) A chimeric toxin vaccine protects against primary and recurrent Clostridium difficile infection. Infect Immun 80: 2678-2688.
36. Yang G, Zhou B, Wang J et al. (2008) Expression of recombinant Clostridium difficile toxin A and B in Bacillus megaterium. BMC Microbiol 8: 192.
37. Zilberberg MD (2009) Clostridium difficile-related hospitalizations among US adults, 2006. Emerg Infect Dis 15: 122-124.