Metabolism of nitro drugs metronidazole and nitazoxanide in Giardia lamblia: Characterization of a novel nitroreductase (GLNR2)

Journal of Antimicrobial Chemotherapy

Volumn 68, Issue 8, 2013, Pages 1781-1789

  Müller, Joachim ^a   Schildknecht, Patricia ^a   Müller, Norbert ^a  

^a UNIVERSITY OF BERN   (Switzerland)

Author keywords

Drug susceptibility; Drug targets; Mode of action

Indexed keywords

ALBENDAZOLE; GLNR1 PROTEIN; GLNR2 PROTEIN; METRONIDAZOLE; NITAZOXANIDE; NITRIC OXIDE; NITROREDUCTASE; UNCLASSIFIED DRUG;

ARTICLE; AXENIC CULTURE; CONTROLLED STUDY; DNA DAMAGE; DNA REPAIR; DRUG METABOLISM; DRUG SENSITIVITY; ESCHERICHIA COLI; GIARDIA LAMBLIA; HETEROLOGOUS EXPRESSION; IN VITRO STUDY; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION;

DRUG SUSCEPTIBILITY; DRUG TARGETS; MODE OF ACTION;

ANTIPROTOZOAL AGENTS; CLONING, MOLECULAR; DNA DAMAGE; ESCHERICHIA COLI; GENE EXPRESSION; GENE EXPRESSION PROFILING; GENES, REPORTER; GIARDIA LAMBLIA; HUMANS; METRONIDAZOLE; NITRIC OXIDE; NITROREDUCTASES; PARASITIC SENSITIVITY TESTS; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; THIAZOLES;

EID: 84880742378     PISSN: 03057453     EISSN: 14602091     Source Type: Journal    
DOI: 10.1093/jac/dkt106     Document Type: Article

References (43)

1. Thompson RCA. Giardiasis as a re-emerging infectious disease and its zoonotic potential. Int J Parasitol 2000; 30: 1259-67.
2. Robertson LJ, Hanevik K, Escobedo AA et al. Giardiasis-why do the symptoms sometimes never stop? Trends Parasitol 2010; 26: 75-82.
3. Wright JM, Dunn LA, Upcroft P et al. Efficacy of antigiardial drugs. Expert Opin Drug Saf 2003; 2: 529-41.
4. Lalle M. Giardiasis in the post genomic era: treatment, drug resistance and novel therapeutic perspectives. Infect Disord Drug Targets 2010; 10: 283-94.
5. Hemphill A, Müller J, Esposito M. Nitazoxanide, a broad-spectrum thiazolide anti-infective agent for the treatment of gastrointestinal infections. Expert Opin Pharmacother 2006; 7: 953-64.
6. Horner DS, Hirt RP, Embley TM. A single eubacterial origin of eukaryotic pyruvate:ferredoxin oxidoreductase genes: implications for the evolution of anaerobic eukaryotes. Mol Biol Evol 1999; 16: 1280-91.
7. Brown DM, Upcroft JA, Edwards MR et al. Anaerobic bacterial metabolism in the ancient eukaryote Giardia duodenalis. Int J Parasitol 1998; 28: 149-64.
8. Upcroft P, Upcroft JA. Drug targets and mechanisms of resistance in the anaerobic protozoa. Clin Microbiol Rev 2001; 14: 150-64.
9. Leitsch D, Kolarich D, Binder M et al. Trichomonas vaginalis: metronidazole and other nitroimidazole drugs are reduced by the flavin enzyme thioredoxin reductase and disrupt the cellular redox system. Implications for nitroimidazole toxicity and resistance. Mol Microbiol 2009; 72: 518-36.
10. Müller J, Ley S, Felger I et al. Identification of differentially expressed genes in a Giardia lamblia WB C6 clone resistant to nitazoxanide and metronidazole. J Antimicrob Chemother 2008; 62: 72-82.
11. Müller J, Sterk M, Hemphill A et al. Characterization of Giardia lamblia WB C6 clones resistant to nitazoxanide and to metronidazole. J Antimicrob Chemother 2007; 60: 280-7.
12. Roldán MD, Pérez-Reinado E, Castillo F et al. Reduction of polynitroaromatic compounds: the bacterial nitroreductases. FEMS Microbiol Rev 2008; 32: 474-500.
13. Johnson GR, Spain JC. Evolution of catabolic pathways for synthetic compounds: bacterial pathways for degradation of 2,4-dinitrotoluene and nitrobenzene. Appl Microbiol Biotechnol 2003; 62: 110-23.
14. Luque-Almagro VM, Blasco R, Paloma Sáez L et al. Interactions between nitrate assimilation and 2,4-dinitrophenol cometabolism in Rhodobacter capsulatus E1F1. Curr Microbiol 2006; 53: 37-42.
15. Nixon JE, Wang A, Field J et al. Evidence for lateral transfer of genes encoding ferredoxins, nitroreductases, NADH oxidase, and alcohol dehydrogenase 3 from anaerobic prokaryotes to Giardia lamblia and Entamoeba histolytica. Eukaryot Cell 2002; 1: 181-90.
16. Müller J, Wastling J, Sanderson S et al. A novel Giardia lamblia nitroreductase, GlNR1, interacts with nitazoxanide and other thiazolides. Antimicrob Agents Chemother 2007; 51: 1979-86.
17. Nillius D, Müller J, Müller N. Nitroreductase (GlNR1) increases susceptibility of Giardia lamblia and Escherichia coli to nitro drugs. J Antimicrob Chemother 2011; 66: 1029-35.
18. D'Autréaux B, Tucker NP, Dixon R et al. A non-haem iron centre in the transcription factor NorR senses nitric oxide. Nature 2005; 437: 769-72.
19. Baptista JM, Justino MC, Melo AM et al. Oxidative stress modulates the nitric oxide defense promoted by Escherichia coli flavorubredoxin. J Bacteriol 2012; 194: 3611-7.
20. Zenno S, Koike H, Kumar AN et al. Biochemical characterization of NfsA, the Escherichia coli major nitroreductase exhibiting a high amino acid sequence homology to Frp, a Vibrio harveyi flavin oxidoreductase. J Bacteriol 1996; 178: 4508-14.
21. Zenno S, Koike H, Tanokura M et al. Gene cloning, purification, and characterization of NfsB, a minor oxygen-insensitive nitroreductase from Escherichia coli, similar in biochemical properties to FRase I, the major flavin reductase in Vibrio fischeri. J Biochem 1996; 120: 736-44.
22. Prosser GA, Copp JN, Syddall SP et al. Discovery and evaluation of Escherichia coli nitroreductases that activate the anti-cancer prodrug CB1954. Biochem Pharmacol 2010; 79: 678-87.
23. Dunn LA, Burgess AG, Krauer KG et al. A new-generation 5-nitroimidazole can induce highly metronidazole-resistant Giardia lamblia in vitro. Int J Antimicrob Agents 2010; 36: 37-42.
24. Müller J, Nillius D, Hehl A et al. Stable expression of Escherichia coli b-glucuronidase A (GusA) in Giardia lamblia: application to high-throughput drug susceptibility testing. J Antimicrob Chemother 2009; 64: 1187-91.
25. Jiménez-Garćia LF, Zavala G, Chávez-Mungúia B et al. Identification of nucleoli in the early branching protist Giardia duodenalis. Int J Parasitol 2008; 38: 1297-304.
26. Spiliotis M. Inverse fusion PCR cloning. PloS ONE 2012; 7: e35407.
27. Griffith KL, Wolf REJ. Measuring b-galactosidase activity in bacteria: cell growth, permeabilization, and enzyme assays in 96-well arrays. Biochem Biophys Res Commun 2002; 290: 397-402.
28. R Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing, 2012.
29. Docampo R, Moreno SN. Free radical metabolites in the mode of action of chemotherapeutic agents and phagocytic cells on Trypanosoma cruzi. Rev Infect Dis 1984; 6: 223-38.
30. Moreno SN, Docampo R. Mechanism of toxicity of nitro compounds used in the chemotherapy of trichomoniasis. Environ Health Perspect 1985; 64: 199-208.
31. Sisson G, Jeong JY, Goodwin A et al. Metronidazole activation is mutagenic and causes DNA fragmentation in Helicobacter pylori and in Escherichia coli containing a cloned H. pylori RdxA(+) (nitroreductase) gene. J Bacteriol 2000; 182: 5091-6.
32. Kutty R, Bennett GN. Biochemical characterization of trinitrotoluene transforming oxygen-insensitive nitroreductases from Clostridium acetobutylicum ATCC 824. Arch Microbiol 2005; 184: 158-67.
33. Valle A, Le Borgne S, Boĺivar J et al. Study of the role played by NfsA, NfsB nitroreductase and NemA flavin reductase from Escherichia coli in the conversion of ethyl 2-(2'-nitrophenoxy)acetate to 4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one (D-DIBOA), a benzohydroxamic acid with interesting biological properties. Appl Microbiol Biotechnol 2012; 94: 163-71.
34. Olekhnovich IN, Goodwin A, Hoffman PS. Characterization of the NAD(P)H oxidase and metronidazole reductase activities of the RdxA nitroreductase of Helicobacter pylori. FEBS J 2009; 276: 3354-64.
35. Vine CE, Cole JA. Unresolved sources, sinks, and pathways for the recovery of enteric bacteria from nitrosative stress. FEMS Microbiol Lett 2011; 325: 99-107.
36. Bowman LA, McLean S, Poole RK et al. The diversity of microbial responses to nitric oxide and agents of nitrosative stress close cousins but not identical twins. Adv Microb Physiol 2011; 59: 135-219.
37. Salzmann A, Denenberg AG, Ueta I et al. Induction and activity of nitric oxide synthase in cultured human intestinal epithelial monolayers. Am J Physiol 1996; 270: 565-73.
38. Eckmann L, Laurent F, Langford TD et al. Nitric oxide production by human intestinal epithelial cells and competition for arginine as potential determinants of host defense against the lumen-dwelling pathogen Giardia lamblia. J Immunol 2000; 164: 1478-87.
39. Ringqvist E, Palm JE, Skarin H et al. Release of metabolic enzymes by Giardia in response to interaction with intestinal epithelial cells. Mol Biochem Parasitol 2008; 159: 85-91.
40. Stadelmann B, Merino MC, Persson L et al. Arginine consumption by the intestinal parasite Giardia intestinalis reduces proliferation of intestinal epithelial cells. PloS ONE 2012; 7: e45325.
41. Kuhnle G, Story GW, Reda T et al. Diet-induced endogenous formation of nitroso compounds in the GI tract. Free Radic Biol Med 2007; 43: 1040-7.
42. Casella L, Monzani E, Roncone R et al. Formation of reactive nitrogen species at biologic heme centers: a potential mechanism of nitric oxide-dependent toxicity. Environ Health Perspect 2002; 110: 709-11.
43. Pullan ST, Monk CE, Lee L et al. Microbial responses to nitric oxide and nitrosative stress: growth, "omic", and physiological methods. Methods Enzymol 2008; 437: 499-519.