This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Horsburgh, M. J.
Right arrow Articles by Foster, S. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Horsburgh, M. J.
Right arrow Articles by Foster, S. J.

 Previous Article  |  Next Article 

Journal of Bacteriology, January 2001, p. 468-475, Vol. 183, No. 2
0021-9193/01/$04.00+0   DOI: 10.1128/JB.183.2.468-475.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

In Staphylococcus aureus, Fur Is an Interactive Regulator with PerR, Contributes to Virulence, and Is Necessary for Oxidative Stress Resistance through Positive Regulation of Catalase and Iron Homeostasis

Malcolm J. Horsburgh,1 Eileen Ingham,2 and Simon J. Foster1,*

Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN,1 and Department of Microbiology, University of Leeds, Leeds,2 England

Received 26 July 2000/Accepted 23 October 2000

The Staphylococcus aureus genome encodes three ferric uptake repressor (Fur) homologues: Fur, PerR, and Zur. To determine the exact role of Fur in S. aureus, we inactivated the fur gene by allelic replacement using a tetracycline resistance cassette, creating strain MJH010 (fur). The mutant had a growth defect in rich medium, and this defect was exacerbated in metal-depleted CL medium. This growth defect was partially suppressed by manganous ion, a metal ion with known antioxidant properties. This suggests that the fur mutation leads to an oxidative stress condition. Indeed, MJH010 (fur) has reduced levels of catalase activity resulting from decreased katA transcription. Using a katA-lacZ fusion we have determined that Fur functions, either directly or indirectly, as an iron-dependent positive regulator of katA expression. Transcription of katA is coregulated by Fur and PerR, since in MJH010 (fur) transcription was still repressed by manganese while transcription in MJH201 (fur perR) was unresponsive to the presence of iron or manganese. Siderophore biosynthesis was repressed by iron in 8325-4 (wild-type) but in MJH010 (fur) was constitutive. A number of putative Fur-regulated genes were identified in the incomplete genome databases using known S. aureus Fur box sequences. Of those tested, the sstABCD and sirABC operons and the fhuD2 and orf4 genes were found to have Fur-regulated expression. MJH010 (fur) was attenuated (P < 0.04) in a murine skin abscess model of infection, as was double-mutant MJH201 (fur perR) (P < 0.03). This demonstrates the importance in vivo of iron homeostasis and oxidative stress resistance regulation in S. aureus.

* Corresponding author. Mailing address: Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield S10 2TN, England. Phone: 44 0114 222 4411. Fax: 44 0114 272 8697. E-mail: S.Foster{at}sheffield.ac.uk.

Journal of Bacteriology, January 2001, p. 468-475, Vol. 183, No. 2
0021-9193/01/$04.00+0   DOI: 10.1128/JB.183.2.468-475.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Zhu, Y., Xiong, Y. Q., Sadykov, M. R., Fey, P. D., Lei, M. G., Lee, C. Y., Bayer, A. S., Somerville, G. A. (2009). Tricarboxylic Acid Cycle-Dependent Attenuation of Staphylococcus aureus In Vivo Virulence by Selective Inhibition of Amino Acid Transport. Infect. Immun. 77: 4256-4264 [Abstract] [Full Text]  
  • da Silva Neto, J. F., Braz, V. S., Italiani, V. C. S., Marques, M. V. (2009). Fur controls iron homeostasis and oxidative stress defense in the oligotrophic alpha-proteobacterium Caulobacter crescentus. Nucleic Acids Res 37: 4812-4825 [Abstract] [Full Text]  
  • Carpenter, B. M., Whitmire, J. M., Merrell, D. S. (2009). This Is Not Your Mother's Repressor: the Complex Role of Fur in Pathogenesis. Infect. Immun. 77: 2590-2601 [Full Text]  
  • Somerville, G. A., Proctor, R. A. (2009). At the Crossroads of Bacterial Metabolism and Virulence Factor Synthesis in Staphylococci. Microbiol. Mol. Biol. Rev. 73: 233-248 [Abstract] [Full Text]  
  • Clarke, S. R., Andre, G., Walsh, E. J., Dufrene, Y. F., Foster, T. J., Foster, S. J. (2009). Iron-Regulated Surface Determinant Protein A Mediates Adhesion of Staphylococcus aureus to Human Corneocyte Envelope Proteins. Infect. Immun. 77: 2408-2416 [Abstract] [Full Text]  
  • Ballal, A., Manna, A. C. (2009). Regulation of Superoxide Dismutase (sod) Genes by SarA in Staphylococcus aureus. J. Bacteriol. 191: 3301-3310 [Abstract] [Full Text]  
  • Davis, L. M., Kakuda, T., DiRita, V. J. (2009). A Campylobacter jejuni znuA Orthologue Is Essential for Growth in Low-Zinc Environments and Chick Colonization. J. Bacteriol. 191: 1631-1640 [Abstract] [Full Text]  
  • Hochgrafe, F., Wolf, C., Fuchs, S., Liebeke, M., Lalk, M., Engelmann, S., Hecker, M. (2008). Nitric Oxide Stress Induces Different Responses but Mediates Comparable Protein Thiol Protection in Bacillus subtilis and Staphylococcus aureus. J. Bacteriol. 190: 4997-5008 [Abstract] [Full Text]  
  • Agarwal, S., Sebastian, S., Szmigielski, B., Rice, P. A., Genco, C. A. (2008). Expression of the Gonococcal Global Regulatory Protein Fur and Genes Encompassing the Fur and Iron Regulon during In Vitro and In Vivo Infection in Women. J. Bacteriol. 190: 3129-3139 [Abstract] [Full Text]  
  • Clarke, S. R., Foster, S. J. (2008). IsdA Protects Staphylococcus aureus against the Bactericidal Protease Activity of Apolactoferrin. Infect. Immun. 76: 1518-1526 [Abstract] [Full Text]  
  • Johnson, M., Cockayne, A., Morrissey, J. A. (2008). Iron-Regulated Biofilm Formation in Staphylococcus aureus Newman Requires ica and the Secreted Protein Emp. Infect. Immun. 76: 1756-1765 [Abstract] [Full Text]  
  • Palazzolo-Ballance, A. M., Reniere, M. L., Braughton, K. R., Sturdevant, D. E., Otto, M., Kreiswirth, B. N., Skaar, E. P., DeLeo, F. R. (2008). Neutrophil Microbicides Induce a Pathogen Survival Response in Community-Associated Methicillin-Resistant Staphylococcus aureus. J. Immunol. 180: 500-509 [Abstract] [Full Text]  
  • Schlag, S., Nerz, C., Birkenstock, T. A., Altenberend, F., Gotz, F. (2007). Inhibition of Staphylococcal Biofilm Formation by Nitrite. J. Bacteriol. 189: 7911-7919 [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]  
  • Cosgrove, K., Coutts, G., Jonsson, I.-M., Tarkowski, A., Kokai-Kun, J. F., Mond, J. J., Foster, S. J. (2007). Catalase (KatA) and Alkyl Hydroperoxide Reductase (AhpC) Have Compensatory Roles in Peroxide Stress Resistance and Are Required for Survival, Persistence, and Nasal Colonization in Staphylococcus aureus. J. Bacteriol. 189: 1025-1035 [Abstract] [Full Text]  
  • Torres, V. J., Pishchany, G., Humayun, M., Schneewind, O., Skaar, E. P. (2006). Staphylococcus aureus IsdB Is a Hemoglobin Receptor Required for Heme Iron Utilization. J. Bacteriol. 188: 8421-8429 [Abstract] [Full Text]  
  • Bjur, E., Eriksson-Ygberg, S., Aslund, F., Rhen, M. (2006). Thioredoxin 1 Promotes Intracellular Replication and Virulence of Salmonella enterica Serovar Typhimurium. Infect. Immun. 74: 5140-5151 [Abstract] [Full Text]  
  • Hyde, J. A., Seshu, J., Skare, J. T. (2006). Transcriptional profiling of Borrelia burgdorferi containing a unique bosR allele identifies a putative oxidative stress regulon.. Microbiology 152: 2599-2609 [Abstract] [Full Text]  
  • Michel, A., Agerer, F., Hauck, C. R., Herrmann, M., Ullrich, J., Hacker, J., Ohlsen, K. (2006). Global Regulatory Impact of ClpP Protease of Staphylococcus aureus on Regulons Involved in Virulence, Oxidative Stress Response, Autolysis, and DNA Repair.. J. Bacteriol. 188: 5783-5796 [Abstract] [Full Text]  
  • Morikawa, K., Ohniwa, R. L., Kim, J., Maruyama, A., Ohta, T., Takeyasu, K. (2006). Bacterial nucleoid dynamics: oxidative stress response in Staphylococcus aureus. GENES CELLS 11: 409-423 [Abstract] [Full Text]  
  • Maalej, S., Dammak, I., Dukan, S. (2006). The impairment of superoxide dismutase coordinates the derepression of the PerR regulon in the response of Staphylococcus aureus to HOCl stress.. Microbiology 152: 855-861 [Abstract] [Full Text]  
  • Marraffini, L. A., DeDent, A. C., Schneewind, O. (2006). Sortases and the Art of Anchoring Proteins to the Envelopes of Gram-Positive Bacteria. Microbiol. Mol. Biol. Rev. 70: 192-221 [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]  
  • Johnson, M., Cockayne, A., Williams, P. H., Morrissey, J. A. (2005). Iron-Responsive Regulation of Biofilm Formation in Staphylococcus aureus Involves Fur-Dependent and Fur-Independent Mechanisms. J. Bacteriol. 187: 8211-8215 [Abstract] [Full Text]  
  • Bates, C. S., Toukoki, C., Neely, M. N., Eichenbaum, Z. (2005). Characterization of MtsR, a New Metal Regulator in Group A Streptococcus, Involved in Iron Acquisition and Virulence. Infect. Immun. 73: 5743-5753 [Abstract] [Full Text]  
  • Jacobsen, I., Gerstenberger, J., Gruber, A. D., Bosse, J. T., Langford, P. R., Hennig-Pauka, I., Meens, J., Gerlach, G.-F. (2005). Deletion of the Ferric Uptake Regulator Fur Impairs the In Vitro Growth and Virulence of Actinobacillus pleuropneumoniae. Infect. Immun. 73: 3740-3744 [Abstract] [Full Text]  
  • Harvie, D. R., Vilchez, S., Steggles, J. R., Ellar, D. J. (2005). Bacillus cereus Fur regulates iron metabolism and is required for full virulence. Microbiology 151: 569-577 [Abstract] [Full Text]  
  • Parker, D., Kennan, R. M., Myers, G. S., Paulsen, I. T., Rood, J. I. (2005). Identification of a Dichelobacter nodosus Ferric Uptake Regulator and Determination of Its Regulatory Targets. J. Bacteriol. 187: 366-375 [Abstract] [Full Text]  
  • Wang, L., Trawick, J. D., Yamamoto, R., Zamudio, C. (2004). Genome-wide operon prediction in Staphylococcus aureus. Nucleic Acids Res 32: 3689-3702 [Abstract] [Full Text]  
  • Needham, A. J., Kibart, M., Crossley, H., Ingham, P. W., Foster, S. J. (2004). Drosophila melanogaster as a model host for Staphylococcus aureus infection. Microbiology 150: 2347-2355 [Abstract] [Full Text]  
  • Alkema, W. B.L., Lenhard, B., Wasserman, W. W. (2004). Regulog Analysis: Detection of Conserved Regulatory Networks Across Bacteria: Application to Staphylococcus aureus. Genome Res 14: 1362-1373 [Abstract] [Full Text]  
  • Li, H., Singh, A. K., McIntyre, L. M., Sherman, L. A. (2004). Differential Gene Expression in Response to Hydrogen Peroxide and the Putative PerR Regulon of Synechocystis sp. Strain PCC 6803. J. Bacteriol. 186: 3331-3345 [Abstract] [Full Text]  
  • Rea, R. B., Gahan, C. G. M., Hill, C. (2004). Disruption of Putative Regulatory Loci in Listeria monocytogenes Demonstrates a Significant Role for Fur and PerR in Virulence. Infect. Immun. 72: 717-727 [Abstract] [Full Text]  
  • Morrissey, J. A., Cockayne, A., Brummell, K., Williams, P. (2004). The Staphylococcal Ferritins Are Differentially Regulated in Response to Iron and Manganese and via PerR and Fur. Infect. Immun. 72: 972-979 [Abstract] [Full Text]  
  • Dale, S. E., Doherty-Kirby, A., Lajoie, G., Heinrichs, D. E. (2004). Role of Siderophore Biosynthesis in Virulence of Staphylococcus aureus: Identification and Characterization of Genes Involved in Production of a Siderophore. Infect. Immun. 72: 29-37 [Abstract] [Full Text]  
  • Shaw, L., Golonka, E., Potempa, J., Foster, S. J. (2004). The role and regulation of the extracellular proteases of Staphylococcus aureus. Microbiology 150: 217-228 [Abstract] [Full Text]  
  • Karavolos, M. H., Horsburgh, M. J., Ingham, E., Foster, S. J. (2003). Role and regulation of the superoxide dismutases of Staphylococcus aureus. Microbiology 149: 2749-2758 [Abstract] [Full Text]  
  • Furano, K., Campagnari, A. A. (2003). Inactivation of the Moraxella catarrhalis 7169 Ferric Uptake Regulator Increases Susceptibility to the Bactericidal Activity of Normal Human Sera. Infect. Immun. 71: 1843-1848 [Abstract] [Full Text]  
  • Mazmanian, S. K., Skaar, E. P., Gaspar, A. H., Humayun, M., Gornicki, P., Jelenska, J., Joachmiak, A., Missiakas, D. M., Schneewind, O. (2003). Passage of Heme-Iron Across the Envelope of Staphylococcus aureus. Science 299: 906-909 [Abstract] [Full Text]  
  • Maruyama, A., Kumagai, Y., Morikawa, K., Taguchi, K., Hayashi, H., Ohta, T. (2003). Oxidative-stress-inducible qorA encodes an NADPH-dependent quinone oxidoreductase catalysing a one-electron reduction in Staphylococcus aureus. Microbiology 149: 389-398 [Abstract] [Full Text]  
  • Schmitt, M. P. (2002). Analysis of a DtxR-Like Metalloregulatory Protein, MntR, from Corynebacterium diphtheriae That Controls Expression of an ABC Metal Transporter by an Mn2+-Dependent Mechanism. J. Bacteriol. 184: 6882-6892 [Abstract] [Full Text]  
  • Harris, A. G., Hinds, F. E., Beckhouse, A. G., Kolesnikow, T., Hazell, S. L. (2002). Resistance to hydrogen peroxide in Helicobacter pylori: role of catalase (KatA) and Fur, and functional analysis of a novel gene product designated 'KatA-associated protein', KapA (HP0874). Microbiology 148: 3813-3825 [Abstract] [Full Text]  
  • Horsburgh, M. J., Aish, J. L., White, I. J., Shaw, L., Lithgow, J. K., Foster, S. J. (2002). {sigma}B Modulates Virulence Determinant Expression and Stress Resistance: Characterization of a Functional rsbU Strain Derived from Staphylococcus aureus 8325-4. J. Bacteriol. 184: 5457-5467 [Abstract] [Full Text]  
  • Ricci, S., Janulczyk, R., Bjorck, L. (2002). The Regulator PerR Is Involved in Oxidative Stress Response and Iron Homeostasis and Is Necessary for Full Virulence of Streptococcus pyogenes. Infect. Immun. 70: 4968-4976 [Abstract] [Full Text]  
  • Morrissey, J. A., Cockayne, A., Hammacott, J., Bishop, K., Denman-Johnson, A., Hill, P. J., Williams, P. (2002). Conservation, Surface Exposure, and In Vivo Expression of the Frp Family of Iron-Regulated Cell Wall Proteins in Staphylococcus aureus. Infect. Immun. 70: 2399-2407 [Abstract] [Full Text]  
  • Smoot, J. C., Barbian, K. D., Van Gompel, J. J., Smoot, L. M., Chaussee, M. S., Sylva, G. L., Sturdevant, D. E., Ricklefs, S. M., Porcella, S. F., Parkins, L. D., Beres, S. B., Campbell, D. S., Smith, T. M., Zhang, Q., Kapur, V., Daly, J. A., Veasy, L. G., Musser, J. M. (2002). Genome sequence and comparative microarray analysis of serotype M18 group A Streptococcus strains associated with acute rheumatic fever outbreaks. Proc. Natl. Acad. Sci. USA 10.1073/pnas.062526099v1 [Abstract] [Full Text]  
  • Milano, A., Forti, F., Sala, C., Riccardi, G., Ghisotti, D. (2001). Transcriptional Regulation of furA and katG upon Oxidative Stress in Mycobacterium smegmatis. J. Bacteriol. 183: 6801-6806 [Abstract] [Full Text]  
  • Barriere, C., Bruckner, R., Talon, R. (2001). Characterization of the Single Superoxide Dismutase of Staphylococcus xylosus. Appl. Environ. Microbiol. 67: 4096-4104 [Abstract] [Full Text]  
  • Sebulsky, M. T., Heinrichs, D. E. (2001). Identification and Characterization of fhuD1 and fhuD2, Two Genes Involved in Iron-Hydroxamate Uptake in Staphylococcus aureus. J. Bacteriol. 183: 4994-5000 [Abstract] [Full Text]  
  • Delany, I., Pacheco, A. B. F., Spohn, G., Rappuoli, R., Scarlato, V. (2001). Iron-Dependent Transcription of the frpB Gene of Helicobacter pylori Is Controlled by the Fur Repressor Protein. J. Bacteriol. 183: 4932-4937 [Abstract] [Full Text]  
  • Wiltshire, M. D., Foster, S. J. (2001). Identification and Analysis of Staphylococcus aureus Components Expressed by a Model System of Growth in Serum. Infect. Immun. 69: 5198-5202 [Abstract] [Full Text]  
  • Horsburgh, M. J., Clements, M. O., Crossley, H., Ingham, E., Foster, S. J. (2001). PerR Controls Oxidative Stress Resistance and Iron Storage Proteins and Is Required for Virulence in Staphylococcus aureus. Infect. Immun. 69: 3744-3754 [Abstract] [Full Text]  
  • Lindsay, J. A., Foster, S. J. (2001). zur: a Zn2+-responsive regulatory element of Staphylococcus aureus. Microbiology 147: 1259-1266 [Abstract] [Full Text]  
  • Mazmanian, S. K., Ton-That, H., Su, K., Schneewind, O. (2002). An iron-regulated sortase anchors a class of surface protein during Staphylococcus aureus pathogenesis. Proc. Natl. Acad. Sci. USA 99: 2293-2298 [Abstract] [Full Text]  
  • Smoot, J. C., Barbian, K. D., Van Gompel, J. J., Smoot, L. M., Chaussee, M. S., Sylva, G. L., Sturdevant, D. E., Ricklefs, S. M., Porcella, S. F., Parkins, L. D., Beres, S. B., Campbell, D. S., Smith, T. M., Zhang, Q., Kapur, V., Daly, J. A., Veasy, L. G., Musser, J. M. (2002). Genome sequence and comparative microarray analysis of serotype M18 group A Streptococcus strains associated with acute rheumatic fever outbreaks. Proc. Natl. Acad. Sci. USA 99: 4668-4673 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»