This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ernst, F. D. Articles by van Vliet, A. H. M. Search for Related Content PubMed PubMed Citation Articles by Ernst, F. D. Articles by van Vliet, A. H. M.

 Previous Article  |  Next Article 

Journal of Bacteriology, June 2005, p. 3687-3692, Vol. 187, No. 11
0021-9193/05/$08.00+0     doi:10.1128/JB.187.11.3687-3692.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Iron-Responsive Regulation of the Helicobacter pylori Iron-Cofactored Superoxide Dismutase SodB Is Mediated by Fur

Florian D. Ernst,^1,2,3 Georg Homuth,^3, Jeroen Stoof,¹ Ulrike Mäder,^3, Barbara Waidner,² Ernst J. Kuipers,¹ Manfred Kist,² Johannes G. Kusters,¹ Stefan Bereswill,^2, and Arnoud H. M. van Vliet^1*

Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands,¹ Department of Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University Hospital of Freiburg, Freiburg, Germany,² Institut für Mikrobiologie und Molekularbiologie, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Germany³

Received 18 September 2004/ Accepted 16 February 2005

Maintaining iron homeostasis is a necessity for all living organisms, as free iron augments the generation of reactive oxygen species like superoxide anions, at the risk of subsequent lethal cellular damage. The iron-responsive regulator Fur controls iron metabolism in many bacteria, including the important human pathogen Helicobacter pylori, and thus is directly or indirectly involved in regulation of oxidative stress defense. Here we demonstrate that Fur is a direct regulator of the H. pylori iron-cofactored superoxide dismutase SodB, which is essential for the defense against toxic superoxide radicals. Transcription of the sodB gene was iron induced in H. pylori wild-type strain 26695, resulting in expression of the SodB protein in iron-replete conditions but an absence of expression in iron-restricted conditions. Mutation of the fur gene resulted in constitutive, iron-independent expression of SodB. Recombinant H. pylori Fur protein bound with low affinity to the sodB promoter region, but addition of the iron substitute Mn²⁺ abolished binding. The operator sequence of the iron-free form of Fur, as identified by DNase I footprinting, was located directly upstream of the sodB gene at positions –5 to –47 from the transcription start site. The direct role of Fur in regulation of the H. pylori sodB gene contrasts with the small-RNA-mediated sodB regulation observed in Escherichia coli. In conclusion, H. pylori Fur is a versatile regulator involved in many pathways essential for gastric colonization, including superoxide stress defense.

Present address: School of Cell and Molecular Biosciences, Newcastle University Medical School, Newcastle-upon-Tyne, United Kingdom.

Present address: Institut für Mikrobiologie und Hygiene, Campus Charité Mitte, Berlin, Germany.

This article has been cited by other articles:

• Zaini, P. A., Fogaca, A. C., Lupo, F. G. N., Nakaya, H. I., Vencio, R. Z. N., da Silva, A. M. (2008). The Iron Stimulon of Xylella fastidiosa Includes Genes for Type IV Pilus and Colicin V-Like Bacteriocins. J. Bacteriol. 190: 2368-2378 [Abstract] [Full Text]  
• Bender, K. S., Yen, H.-C. B., Hemme, C. L., Yang, Z., He, Z., He, Q., Zhou, J., Huang, K. H., Alm, E. J., Hazen, T. C., Arkin, A. P., Wall, J. D. (2007). Analysis of a Ferric Uptake Regulator (Fur) Mutant of Desulfovibrio vulgaris Hildenborough. Appl. Environ. Microbiol. 73: 5389-5400 [Abstract] [Full Text]  
• Kitphati, W., Ngok-ngam, P., Suwanmaneerat, S., Sukchawalit, R., Mongkolsuk, S. (2007). Agrobacterium tumefaciens fur Has Important Physiological Roles in Iron and Manganese Homeostasis, the Oxidative Stress Response, and Full Virulence. Appl. Environ. Microbiol. 73: 4760-4768 [Abstract] [Full Text]  
• Belzer, C., van Schendel, B. A. M., Kuipers, E. J., Kusters, J. G., van Vliet, A. H. M. (2007). Iron-Responsive Repression of Urease Expression in Helicobacter hepaticus Is Mediated by the Transcriptional Regulator Fur. Infect. Immun. 75: 745-752 [Abstract] [Full Text]  
• Ernst, F. D., Stoof, J., Horrevoets, W. M., Kuipers, E. J., Kusters, J. G., van Vliet, A. H. M. (2006). NikR Mediates Nickel-Responsive Transcriptional Repression of the Helicobacter pylori Outer Membrane Proteins FecA3 (HP1400) and FrpB4 (HP1512). Infect. Immun. 74: 6821-6828 [Abstract] [Full Text]  
• Alamuri, P., Maier, R. J. (2006). Methionine Sulfoxide Reductase in Helicobacter pylori: Interaction with Methionine-Rich Proteins and Stress-Induced Expression.. J. Bacteriol. 188: 5839-5850 [Abstract] [Full Text]  
• Kusters, J. G., van Vliet, A. H. M., Kuipers, E. J. (2006). Pathogenesis of Helicobacter pylori Infection. Clin. Microbiol. Rev. 19: 449-490 [Abstract] [Full Text]  
• Alamuri, P., Mehta, N., Burk, A., Maier, R. J. (2006). Regulation of the Helicobacter pylori Fe-S Cluster Synthesis Protein NifS by Iron, Oxidative Stress Conditions, and Fur.. J. Bacteriol. 188: 5325-5330 [Abstract] [Full Text]  
• Gancz, H., Censini, S., Merrell, D. S. (2006). Iron and pH Homeostasis Intersect at the Level of Fur Regulation in the Gastric Pathogen Helicobacter pylori. Infect. Immun. 74: 602-614 [Abstract] [Full Text]  
• Mey, A. R., Wyckoff, E. E., Kanukurthy, V., Fisher, C. R., Payne, S. M. (2005). Iron and Fur Regulation in Vibrio cholerae and the Role of Fur in Virulence. Infect. Immun. 73: 8167-8178 [Abstract] [Full Text]  
• Ernst, F. D., Kuipers, E. J., Heijens, A., Sarwari, R., Stoof, J., Penn, C. W., Kusters, J. G., van Vliet, A. H. M. (2005). The Nickel-Responsive Regulator NikR Controls Activation and Repression of Gene Transcription in Helicobacter pylori. Infect. Immun. 73: 7252-7258 [Abstract] [Full Text]