Journal of Microbiology and Biotechnology
The Korean Society for Microbiology and Biotechnology publishes the Journal of Microbiology and Biotechnology.

2016 ; Vol.26-4: 693~699

AuthorLi Fang Lu, Dae Hong Kim, Ik Hwan Lee, Ji Hong, Peng Zhang, I Na Yoon, Jae Sam Hwang, Ho Kim
Place of dutyDepartment of Life Science, College of Natural Science, Daejin University, Pocheon 11159, Republic of Korea,Hainan Institute of Science and Technology, Haikou 571126, P.R. China
TitlePotassium Acetate Blocks Clostridium difficile Toxin A-Induced Microtubule Disassembly by Directly Inhibiting Histone Deacetylase 6, Thereby Ameliorating Inflammatory Responses in the Gut
PublicationInfo J. Microbiol. Biotechnol.2016 ; Vol.26-4
AbstractClostridium difficile toxin A is known to cause deacetylation of tubulin proteins, which blocks microtubule formation and triggers barrier dysfunction in the gut. Based on our previous finding that the Clostridium difficile toxin A-dependent activation of histone deacetylase 6 (HDAC-6) is responsible for tubulin deacetylation and subsequent microtubule disassembly, we herein examined the possible effect of potassium acetate (PA; whose acetyl group prevents the binding of tubulin to HDAC-6) as a competitive/false substrate. Our results revealed that PA inhibited toxin A-induced deacetylation of tubulin and recovered toxin A-induced microtubule disassembly. In addition, PA treatment significantly decreased the production of IL-6 (a marker of inflamed tissue) in the toxin A-induced mouse enteritis model. An in vitro HDAC assay revealed that PA directly inhibited HDAC-6-mediated tubulin deacetylation, indicating that PA acted as a false substrate for HDAC-6. These results collectively indicate that PA treatment inhibits HDAC-6, thereby reducing the cytotoxicity and inflammatory responses caused by C. difficile toxin A.
Full-Text
Key_wordClostridium difficile toxin A, colitis, microtubule assembly with tubulin, potassium acetate, enteritis, histone deacetylase 6
References
  1. Arregui L, Munoz-Fontela C, Serrano S, Barasoain I, Guinea A. 2002. Direct visualization of the microtubular cytoskeleton of ciliated protozoa with a fluorescent taxoid. J. Eukaryot. Microbiol. 49: 312-318.
    Pubmed CrossRef
  2. Dhanya K, Kizhakkayil J, Syamkumar S, Sasikumar B. 2007. Isolation and amplification of genomic DNA from recalcitrant dried berries of black pepper (Piper nigrum L.) - a medicinal spice. Mol. Biotechnol. 37: 165-168.
    Pubmed CrossRef
  3. Donet JA, Laconti JJ, Morillas JA, Barkin JA, Barkin JS. 2015. Acute respiratory distress syndrome due to Clostridium difficile colitis: a c ase report and r ev iew of the l iterature. Rev. Gastroenterol. Peru 35: 262-264.
    Pubmed
  4. Dupre-Aucouturier S, Castells J, Freyssenet D, Desplanches D. 1985. Trichostatin A, a histone deacetylase inhibitor, modulates unloaded-induced skeletal muscle atrophy. J. Appl. Physiol. 119: 342-351.
    Pubmed CrossRef
  5. Hato Z, Mako E, Kristof T. 2014. Water-mediated potassium acetate intercalation in kaolinite as revealed by molecular simulation. J. Mol. Model. 20: 2140.
    Pubmed CrossRef
  6. Hecht G, Pothoulakis C, LaMont JT, Madara JL. 1988. Clostridium difficile toxin A perturbs cytoskeletal structure and tight junction permeability of cultured human intestinal epithelial monolayers. J. Clin. Invest. 82: 1516-1524.
    Pubmed CrossRef Pubmed Central
  7. Hubbert C, Guardiola A, Shao R, Kawaguchi Y, Ito A, Nixon A, et al. 2002. HDAC6 is a microtubule-associated deacetylase. Nature 417: 455-458.
    Pubmed CrossRef
  8. 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.
    Pubmed CrossRef
  9. Kelly CP, LaMont JT. 1998. Clostridium difficile infection. Annu. Rev. Med. 49: 375-390.
    Pubmed CrossRef
  10. Kim DH, Lee IH, Nam ST, Nam HJ, Kang JK, Seok H, et al. 2014. Effect of antisera from Clostridium difficile-infected mice on toxin-A-induced colonic epithelial cell death signaling. J. Microbiol. Biotechnol. 24: 696-703.
    Pubmed CrossRef
  11. Kim H, Kokkotou E, Na X, Rhee SH, Moyer MP, Pothoulakis C, et al. 2005. Clostridium difficile toxin A-induced colonocyte apoptosis involves p53-dependent p21(WAF1/CIP1) induction via p38 mitogen-activated protein kinase. Gastroenterology 129: 1875-1888.
    Pubmed CrossRef
  12. Kim H, Rhee SH, Pothoulakis C, Lamont JT. 2009. Clostridium difficile toxin A binds colonocyte Src causing dephosphorylation of focal adhesion kinase and paxillin. Exp. Cell Res. 19: 33363344
    CrossRef
  13. Kin S, Schilling MW, Smith BS, Silva JL, Kim T, Pham AJ, et al. 2011. Potassium acetate and potassium lactate enhance the microbiological and physical properties of marinated catfish fillets. J. Food Sci. 76: S242-S250.
    Pubmed CrossRef
  14. Korac M, Milosevic I, Markovic M, Popovic N, Ilic M, Markovic A, et al. 2015. Clostridium difficile infection: a Serbian single-center experience. J. Infect. Dev. Ctries. 9: 136140.
    Pubmed CrossRef
  15. Krsek M, Wellington EM. 1999. Comparison of different methods for the isolation and purification of total community DNA from soil. J. Microbiol. Methods 39: 1-16.
    CrossRef
  16. Li R, Lu L, Lin Y, Wang M, Liu X. 2015. Efficacy and safety of metronidazole monotherapy versus vancomycin monotherapy or combination therapy in patients with Clostridium difficile infection: a systematic review and meta-analysis. PLoS One 10: e0137252.
    Pubmed CrossRef Pubmed Central
  17. Mahal K, Schruefer S, Steinemann G, Rausch F, Schobert R, Biersack B, et al. 2015. Biological evaluation of 4,5diarylimidazoles with hydroxamic acid appendages as novel dual mode anticancer agents. Cancer Chemother. Pharmacol. 75: 691-700.
    Pubmed CrossRef
  18. Nam HJ, Kang JK, Kim SK, Ahn KJ, Seok H, Park SJ, et al. 2010. Clostridium difficile toxin A decreases acetylation of tubulin, leading to microtubule depolymerization through activation of histone deacetylase 6, and this mediates acute inflammation. J. Biol. Chem. 285: 32888-32896.
    Pubmed CrossRef Pubmed Central
  19. North BJ, Marshall BL, Borra MT, Denu JM, Verdin E. 2003. The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol. Cell 11: 437-444.
    CrossRef
  20. Piperno G, LeDizet M, Chang XJ. 1987. Microtubules containing acetylated alpha-tubulin in mammalian cells in culture. J. Cell Biol. 104: 289-302.
    Pubmed CrossRef
  21. Pothoulakis C, LaMont JT. 1993. Clostridium difficile colitis and diarrhea. Gastroenterol. Clin. North Am. 22: 623-637.
    Pubmed
  22. Pothoulakis C, Lamont JT. 2001. Microbes and microbial toxins: paradigms for microbial-mucosal interactions. II. The integrated response of the intestine to Clostridium difficile toxins. Am. J. Physiol. Gastrointest. Liver Physiol. 280: G178-G183.
    Pubmed
  23. Qiong G, Haihui H. 2015. Update on antimicrobial resistance in Clostridium difficile. Yi Chuan 37: 458-464.
    Pubmed
  24. Reichert V, Moore MJ. 2000. Better conditions for mammalian in vitro splicing provided by acetate and glutamate as potassium counterions. Nucleic Acids Res. 28: 416-423.
    Pubmed CrossRef Pubmed Central
  25. Shan G, Jin W, Lam EK, Xing X. 2008. Purification of total DNA extracted from activated sludge. J. Environ. Sci. 20: 80-87.
    CrossRef
  26. Warny M, Keates AC, Keates S, Castagliuolo I, Zacks JK, Aboudola S, et al. 2 000. p 38MAP kinase a ctiv ation by Clostridium difficile toxin A mediates monocyte necrosis, IL-8 production, and enteritis. J. Clin. Invest. 105: 1147-1156.
    Pubmed CrossRef Pubmed Central
  27. Wolfsdorf J, Glaser N, Sperling MA. 2006. Diabetic ketoacidosis in infants, children, and adolescents: a consensus statement from the American Diabetes Association. Diabetes Care 29:1150-1159.
    Pubmed CrossRef
  28. Zhang Y, Li N, Caron C, Matthias G, Hess D, Khochbin S, et al. 2003. HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo. EMBO J. 22: 1168-1179.
    Pubmed CrossRef Pubmed Central



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