YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Transcriptional Regulatory Protein Fur of Helicobacter pylori and its Role in Metronidazole Resistance

Helicobacter pylori의 전사조절인자인 Fur 단백질과 Metronidazole 저항성

  • Berg, Douglas E. (School of Medicine, Washinghton University) ;
  • Choi, Sung-Sook (School of Pharmacy, Sahmyook University)
  • Published : 2008.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

To clarify effects of the structural changes of Fur protein on the resistance to metronidazole (Mtz), the mutational analysis of structure and function of the protein in Helicobacter pylori (Hp) was undertaken. It was identified that some changes in Hp Fur protein resulted in increase of resistance to Mtz, and other changes resulted in decrease of resistance. Increase of Mtz resistance came from the enzyme's decreased ability of reducing prodrug Mtz to the form of bactericidal agent. Some sites that affects Mtz resistance (i) in Fur's N terminal extension, and (ii) in its central region, which links DNA binding and Fe-binding modules were identified. It was also found that the addition of FLAG tag to Fur's C terminus also significantly impairs Fur function.

Keywords

References

  1. Westblom, J. U., Czinn, S. J. and Nedrud, J. G. (ed.) : Current topics in microbiology and immunology, vol. 241, gastroduodenal disease and Helicobacter pylori: pathology, diagnosis and treatment. Springer Press, Berlin, Germany (1999)
  2. Parsonnet, J. : Helicobacter and gastric adenocarcinoma, pp. 372-408. In J. Personnet (ed.). Microbes and malignancy: Infection as a cause of human cancer. Oxford University Press, New York, N.Y. (1999)
  3. Blaser, M. J. and Berg, D. E. : Helicobacter pylori genetic diversity and risk of human disease. J. Clin. Investig. 107, 767 (2001) https://doi.org/10.1172/JCI12672
  4. Ramarao, N., Gray-Owen, S. D. and Meyer, T. F. : Helicobacter pylori induces but survives the extracellular release of oxygen radical from professional phagocytes using catalase activity. Mol. Microbiol. 38, 103 (2000) https://doi.org/10.1046/j.1365-2958.2000.02114.x
  5. Nardone, G., Rocco, A. and Malfertheiner, P. : Helicobacter pylori and molecular events in precancerous gastric lesions. Aliment. Pharmacol. Ther. 20, 261 (2004) https://doi.org/10.1111/j.1365-2036.2004.02075.x
  6. Hazell, S. L., Harris, A. G. and Trend, M. A. : Evasion of the toxic effects of oxygen. In Helicobacter pylori; physiology and genetics. Mobley, H. L. T., Mendz, G. L. and Hazell, S. L. (eds.). Washington DC; American Society for Microbiology Press, pp. 167-175 (2001)
  7. Tourati, D. : Iron and oxidative stress in bacteria. Arch. Biochem. Biophys. 373, 1(2000) https://doi.org/10.1006/abbi.1999.1518
  8. Andrew, S. C., Robinson, A. K. and Rodriguez-Quinones, F. : Bacterial iron homeostasis. FEMS Microbial. Rev. 27, 215 (2003) https://doi.org/10.1016/S0168-6445(03)00055-X
  9. Bagg, A. and Neidland, J. B. : Ferric uptake regulation protein acts as a repressor, employing iron (II) as a cofactor to bind the operator of an iron transport operon in Escherichia coli. Biochemistry 26, 5471 (1987) https://doi.org/10.1021/bi00391a039
  10. Hanke, K. : Iron and metal regulation in bacteria. Curr. Opion. Microbiol. 4, 172 (2001) https://doi.org/10.1016/S1369-5274(00)00184-3
  11. Florian, D. E., Stefan, B., Barbara, W., Jeroen, S., Ulrike, M., Johannes, G. K., Ernst, J. K., Manfred, K., Aronoud, H. M. van V. and Gerg, H. : Transcriptional profiles of Helicobacter pylori Fur- and iron regulated gene expression. Microbiology 151, 533 (2005) https://doi.org/10.1099/mic.0.27404-0
  12. Hall, H. K. and Foster, J. W. : The role of Fur in the acid tolerance response of Salmonella typhimurium is physiologically separable from its role in iron acquisition. J. Bacteriol. 178, 5683 (1996) https://doi.org/10.1128/jb.178.19.5683-5691.1996
  13. Pohl, E., Haller, C. J., Mijovilovich, A., Meyer-Klaucke, W., Garman, E. and Vasil, L. M. : Architecture of a protein central to iron homeostasis: crystal structure and spectroscopic analysis of the ferric uptake regulator. Molecular Microbiology 47(4), 903 (2003) https://doi.org/10.1046/j.1365-2958.2003.03337.x
  14. Albert, D. T., Dailidien, D., Dalidien, G., Jason E. N., Awdhesh, K., Todd, A. R., Michale, M., Jaz, S., Roland, D. G. and Berg, D. E. : Mutational discovery in bacterial genomes: metronidazole resistance in Helicobacter pylori. Nature Meth. 2, 951 (2005) https://doi.org/10.1038/nmeth805
  15. Garry, S., Avery, G., Ausra, R., Nicky, J. H., Asish, K. M., Berg, D. E. and Hoffman, S. P. : Enzymes associated with reductive activation and action of nitrozoxamide, nitrofurans, and metronidazole in Helicobacter pylori. Antimicrob. Agents Chemother. 146(7), 2116 (2002)
  16. Jeong, J. Y., Mukhopadhyay, A. K., Dailidien, D., Wang, Y., Velapatino, B., Gilman, R. H., Parkinson, A. J., Nair, G. B., Wong, B. Y., Lam, S. K., Mistry, R., Segal, I., Yuan, Y., Gao, H., Alarcon, T., Brea, M. L., Ito, Y., Kersulyte, D., Lee, H. K., Gong, Y., Goodwin, A., Hoffman, P. S. and Berg, D. E. : Sequential inactivation of rdxA (HP0954) and frxA (HP0642) nitroreductase genes cause moderate and high-level metronidazole resistance in Helicobacter pylori. J. Bacteriol. 182(18), 5082 (2000) https://doi.org/10.1128/JB.182.18.5082-5090.2000
  17. Dailidien, D., Chang, D., Dailidien, G. and Berg, E. D. : Finding mutations implicated in Mtz hyperrsistance. Unpublished data
  18. Tan, S. and Berg, E. D. : Motility of urease-deficient derivatives of Helicobacter pylori. J. Bacteriol. 186(3), 885 (2004) https://doi.org/10.1128/JB.186.3.885-888.2004
  19. Dailidien, D., Tan, S., Zhang, O. K., Lee, A. H., Severinor, K. and Berg, E. D. : Urea sensitization caused by separation of Helicobacter pylori RNA polymerase beta and beta' subunit. Helicobacter 12(2), 103 (2007) https://doi.org/10.1111/j.1523-5378.2007.00479.x
  20. Vartanian, J. P., Henrry, M. and Wain-Hobson, S. : Hypermutagenic PCR involving all four transition and a sizeable proportion of transversion. Nucleic Acids Resch. 24, 2627 (1996) https://doi.org/10.1093/nar/24.14.2627
  21. Israel, D. A., Lou, A. S. and Blaser, M. J. : Characteristics of Helicobacter pylori natural transformation. FEMS Microbial. Lett. 186, 275 (2000) https://doi.org/10.1111/j.1574-6968.2000.tb09117.x
  22. Vasil, L. M. and Ochsner, A. U. : The response of Pseudomonas aeruginosa to iron: genetics, biochemistry and virulence. Mol. Microbiol. 34(3), 399 (1999) https://doi.org/10.1046/j.1365-2958.1999.01586.x
  23. Peredo, A. G., Saint-Pierre, C., Latour, J. M., Michaud-Soret, I. and Forest, E. : Conformational changes of the ferric uptake regulation protein upon metal activation and DNA binding; first evidence of structural homologies with the diphtheria toxin repressor. J. Mol. Biol. 310, 83 (2001) https://doi.org/10.1006/jmbi.2001.4769
  24. Delany, I., Sophon, G., Rappuoli, R. and Scarlato, V. : The Fur repressor controls transcription of iron-activated and -repressed genes in Helicobacter pylori. Mol. Microbiol. 42, 1297 (2001) https://doi.org/10.1046/j.1365-2958.2001.02696.x