Antiparasitic drug nitazoxanide inhibits the pyruvate oxidoreductases of Helicobacter pylori, selected anaerobic bacteria and parasites, and Campylobacter jejuni

Antimicrobial Agents and Chemotherapy

Volumn 51, Issue 3, 2007, Pages 868-876

  Hoffman, Paul S ^a,b,c,d,f   Sisson, Gary ^c   Croxen, Matthew A ^a,b,c   Welch, Kevin ^b   Harman, W Dean ^b   Cremades, Nunilo ^e   Morash, Michael G ^c  

^a UNIVERSITY OF VIRGINIA   (United States)

^b UNIVERSITY OF VIRGINIA   (United States)

^c DALHOUSIE UNIVERSITY   (Canada)

^d DALHOUSIE UNIVERSITY   (Canada)

^e UNIVERSITY OF ZARAGOZA   (Spain)

^f UNIVERSITY OF VIRGINIA HEALTH SYSTEM   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYL COENZYME A; CARBON DIOXIDE; DYE; NITAZOXANIDE; PYRUVATE DEHYDROGENASE; PYRUVATE SYNTHASE; PYRUVIC ACID; THIAMINE PYROPHOSPHATASE; THIAZOLE;

ACIDITY; ANAEROBIC BACTERIUM; ARTICLE; CAMPYLOBACTER JEJUNI; CLOSTRIDIUM DIFFICILE; CLOSTRIDIUM PERFRINGENS; DECARBOXYLATION; DRUG STRUCTURE; ENTAMOEBA HISTOLYTICA; ENZYME SUBSTRATE; GENE OVEREXPRESSION; GIARDIA LAMBLIA; HELICOBACTER PYLORI; ION EXCHANGE CHROMATOGRAPHY; MOLECULAR CLONING; NONHUMAN; OPERON; PKA; PRIORITY JOURNAL; PROTEIN PURIFICATION; PROTON TRANSPORT; REACTION ANALYSIS; TRICHOMONAS VAGINALIS;

ACETYL COENZYME A; ANIMALS; ANTIPROTOZOAL AGENTS; BACTERIA, ANAEROBIC; CAMPYLOBACTER JEJUNI; CARBON DIOXIDE; CLONING, MOLECULAR; CLOSTRIDIUM; CULTURE MEDIA; ENZYME INHIBITORS; HELICOBACTER PYLORI; KINETICS; L-LACTATE DEHYDROGENASE; MAGNETIC RESONANCE SPECTROSCOPY; PARASITES; PYRUVATE DEHYDROGENASE COMPLEX; PYRUVIC ACID; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; THIAMINE PYROPHOSPHATE; THIAZOLES;

EID: 33847660062     PISSN: 00664804     EISSN: None     Source Type: Journal    
DOI: 10.1128/AAC.01159-06     Document Type: Article

References (35)

1. Adagu, I. S., D. Nolder, D. C. Warhurst, and J. F. Rossignol. 2002. In vitro activity of nitazoxanide and related compounds against isolates of Giardia intestinalis, Entamoeba histolytica and Trichomonas vaginalis. J. Antimicrob. Ther. 49:103-111.
2. Cavazza, C., C. Contreras-Martel, L. Pieulle, E. Chabriere, E. C. Halchikian, and J. C. Fontecilla-Camps. 2006. Flexibility of thiamine diphosphate revealed by kinetic crystallographic studies of the reaction of pyruvate-ferredoxin oxidoreductase with pyruvate Structure 14:217-224.
3. Chabriere, E., X. Vernede, B. Guigliarelli, M.-H. Charon, E. C. Hatchikian, and J. C. Fontecilla-Camps. 2001. Crystal structure of the free radical intermediate of pyruvate:ferredoxin oxidoreductase. Science 294:2559-2563.
4. Cremades, N., M. Bueno, M. Toja, and J. Sancho. 2005. Towards a new therapeutic target: Helicobacter pylori flavodoxin. Biophys. Chem. 115:267-276.
5. Dubreuil, L., X. Houcke, Y. Mouton, and J. F. Rossignol. 1996. In vitro evaluation of the activities of nitazoxanide and tizoxanide against anaerobes and aerobic organisms. Antimicrob. Agents Chemother. 40:2266-2270.
6. Evans, M. C., B. B. Buchanan, and D. I. Arnon. 1966. A new ferredoxin-dependent carbon reduction cycle in a photosynthetic bacterium. Proc. Natl. Acad. Sci. USA 55:928-934.
7. Furdui, C., and S. W. Ragsdale. 2002. The roles of coenzyme A in the pyruvate:ferredoxin oxidoreductase reaction mechanism: rate enhancement of electron transfer from a radical intermediate to an iron-sulfur cluster. Biochemistry 41:9921-9937.
8. Gilles, H. M., and P. S. Hoffman. 2002. Treatment of intestinal parasitic infections: a review of nitazoxanide. Trends Parasitol. 18:95-97.
9. Goodwin, A., D. Kersulyte, G. Sisson, S. J. O. V. van Zanten, D. E. Berg, and P. S. Hoffman. 1998. Metronidazole resistance in Helicobacter pylori is due to null mutations in a gene (rdxA) that encodes an oxygen-insensitive NADPH nitroreductase. Mol. Microbiol. 28:383-394.
10. Guttner, Y., H. M. Windsor, C. H. Viiala, L. Dusci, and B. J. Marshall. 2003. Nitazoxanide in treatment of Helicobacter pylori: a clinical and in vitro study. Antimicrob. Agents Chemother. 47:3780-3783.
11. Hoffman, P. S., and T. G. Goodman. 1982. Respiratory physiology and energy conservation efficiency of Campylobacter jejuni. J. Bacteriol. 150:319-326.
12. Hoffman, P. S., A. Goodwin, J. Johnsen, K. Magee, and S. J. O. Veldhuyzen van Zanten. 1996. Metabolic activities of metronidazole-sensitive and -resistant strains of Helicobacter pylori: repression of pyruvate oxidoreductase and expression of isocitrate lyase activity correlate with resistance. J. Bacteriol. 178:4822-4829.
13. Horner, D. S., R. P. Hirt, and T. M. Embley. 1999. A single eubacterial origin of eukaryotic pyruvate:ferredoxin oxidoreductase genes: implications for the evolution of anaerobic eukaryotes. Mol. Biol. Evol. 16:1280-1291.
14. Hughes, N. J., P. A. Chalk, C. L. Clayton, and D. J. Kelly. 1995. Identification of carboxylation enzymes and characterization of a novel four-subunit pyruvate:flavodoxin oxidoreductase from Helicobacter pylori. J. Bacteriol. 177:3953-3959.
15. Hughes, N. J., C. L. Clayton, P. A. Chalk, and D. J. Kelly. 1998. Helicobacter pylori porCDAB and oorDABC genes encode distinct pyruvatetflavodoxin and 2-oxoglutarate:acceptor oxidoreductases which mediate electron transport to NADP. J. Bacteriol. 180:1119-1128.
16. Kletzin, A., and M. W. Adams. 1996. Molecular and phylogenetic characterization of pyruvate and 2-ketoisovalerate ferredoxin oxidoreductases from Pyrococcus furiosus and pyruvate ferredoxin oxidoreductase from Thermotoga maritime. J. Bacteriol. 178:248-257.
17. Mahony, D. E., S. Lim-Morrison, L. Bryden, G. Faulkner, P. S. Hoffman, L. Agocs, G. G. Briand, N. Burford, and H. Maguire. 1999. Antimicrobial activity of synthetic bismuth compounds against Clostridium difficile. Antimicrob. Agents Chemother. 43:582-588.
18. Mégraud, F., A. Occhialini, and J. F. Rossignol. 1998. Nitazoxanide, a potential drug to eradicate Helicobacter pylori with no cross resistance to metronidazole. Antimicrob. Agents Chemother. 42:2836-2840.
19. Menon, S., and S. W. Ragsdale. 1996. Unleashing hydrogenase activity in carbon monoxide dehydrogenase/acetyl-CoA synthase and pyruvate:ferredoxin oxidoreductase. Biochemistry 35:15814-15821.
20. Musher, D. M., N. Logan, R. J. Hamill, H. L. Dupont, A. Lentnek, A. Gupta, and J. F. Rossingol. 2006. Nitazoxanide for the treatment of Clostridium difficile colitis. Clin. Infect. Dis. 43:421-427.
21. Ortiz, J. J., N. Lopez Chegne, G. Gargala, and L. Favennec. 2002. Comparative clinical studies of nitazoxanide, albendazole and praziquantel in the treatment of ascariasis, trichuriasis and hymenolepiasis in children from Peru. Trans. R. Soc. Trop. Med. Hyg. 96:193-196.
22. Pankuch, G. A., and P. C. Appelbaum. 2006. Activities of tizoxanide and nitazoxanide compared to those of five other thiazolides and three other agents against anaerobic species. Antimicrob. Agents Chemother. 50:1112-1117.
23. Patel, M. S., and T. E. Roche. 1990. Molecular biology and biochemistry of pyruvate dehydrogenase complexes. FASEB J. 4:3224-3233.
24. Pohl, M., G. A. Sprenger, and M. Muller. 2004. A new perspective on thiamine catalysis. Curr. Opin. Biotechnol. 15:335-342.
25. Ragsdale, S. W. 2003. Pyruvate ferredoxin oxidoreductase and its radical intermediate. Chem. Rev. 103:2333-2346.
26. Rossignol, J. F., M. Abu-Zekry, A. Hussein, and M. G. Santoro. 2006. Effect of nitazoxanide for treatment of severe rotavirus diarrhoea: randomised double-blind placebo-controlled trial. Lancet 368:124-129.
27. Rossignol, J. F., A. Ayoub, and M. S. Ayers. 2001. Treatment of diarrhea caused by Cryptosporidium parvum: a prospective randomized, double-blind, placebo-controlled study of nitazoxanide. J. Infect. Dis. 184:103-106.
28. Sisson, G., A. Goodwill, A. Raudonikiene, N. J. Birks, H. Han, A. Mukhopadhyay, D. E. Berg, and P. S. Hoffman. 2002. Enzymes associated with the reductive activation and action of nitazoxanide, nitrofurans and metronidazole in Helicobacter pylori. Antimicrob. Agents Chemother. 46:2116-2123.
29. + (nitroreductase) gene. J. Bacteriol. 182:5091-5096.
30. Tomb, J.-F., O. White, A. R. Kerlavage, R. A. Clayton, G. G. Sutton, R. D. Fleischmann, K. A. Ketchum, H. P. Klenk, S. Gill, B. A. Dougherty, K. Nelson, J. Quackenbush, L. Zhou, E. F. Kirkness, S. Peterson, B. Loftus, D. Richardson, R. Dodson, H. G. Khalak, A. Glodek, K. McKenney, L. M. Fitzegerald, N. Lee, M. D. Adams, E. K. Hickey, D. E. Berg, J. D. Gocayne, T. R. Utterback, J. D. Peterson, J. M. Kelley, M. D. Cotton, J. M. Weidman, C. Fujii, C. Bowman, L. Watthey, E. Wallin, W. S. Hayes, M. Borodovsky, P. D. Karp, H. O. Smith, C. M. Fraser, and J. C. Venter. 1997. The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature 388:539-547.
31. Townson, S. M., J. A. Upcroft, and P. Upcroft. 1996. Characterization and purification of pyruvate:ferredoxin oxidoreductase from Giardia duodenalis. Mol. Biochem. Parasitol. 79:183-193.
32. Uyeda, K., and J. C. Rabinowitz. 1971. Pyruvate-ferredoxin oxidoreductase. 3. Purification and properties of the enzyme. J. Biol. Chem. 246:3111-3119.
33. Whiteway, J., P. Koziarz, J. Veall, N. Sandhu, P. Kumar, B. Hoecher, and I. B. Lambert. 1998. Oxygen-insensitive nitroreductases: analysis of the roles of nsfA and nfsB in development of resistance to 5-nitrofuran derivatives in Escherichia coli. J. Bacteriol. 180:5529-5539.
34. Yamamoto, Y., A. Hakki, H. Friedman, S. Okubo, T. Shimamura, P. S. Hoffman, and J. F. Rossignol. 1999. Nitazoxanide, a nitrothiazolide anti-parasitic drug, is an anti-Helicobacter pylori agent with anti-vaculating toxin activity. Chemotherapy 45:303-312.
35. Zulu, I., P. Kelly, L. Njobvu, S. Sianongo, K. Kaonga, V. McDonald, M. Farthing, and R. Pollok. 2005. Nitazoxanide for persistent diarrhea in Zambian acquired immune deficiency syndrome patients: a randomized-controlled trial. Aliment. Pharmacol. Ther. 21:757-763.