This Article
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 Hall, H. K.
Right arrow Articles by Foster, J. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hall, H. K.
Right arrow Articles by Foster, J. W.

 Previous Article  |  Next Article 

J. Bacteriol., 10 1996, 5683-5691, Vol 178, No. 19
Copyright © 1996, American Society for Microbiology

The role of fur in the acid tolerance response of Salmonella typhimurium is physiologically and genetically separable from its role in iron acquisition

HK Hall and JW Foster
Department of Microbiology and Immunology, College of Medicine, University of South Alabama, Mobile 36688, USA.

The response of Salmonella typhimurium to low pH includes a low-pH protection system called the acid tolerance response (ATR). The iron- regulatory protein Fur has been implicated in the ATR since fur mutants are acid sensitive and cause altered expression of several acid shock proteins (J. W. Foster, J. Bacteriol. 173:6896-6902, 1991). We have determined that the acid-sensitive phenotype of fur mutations is indeed due to a defect in Fur that can be complemented by a fur(+)-containing plasmid. However, changes in cellular iron status alone did not trigger the ATR. Cells clearly required exposure to low pH in order to induce acid tolerance. The role of Fur in acid tolerance was found to extend beyond regulating iron acquisition. A mutation in fur converting histidine 90 to an arginine (H90R) eliminated Fur-mediated iron regulation of enterochelin production and deregulated an iroA-lacZ fusion but had no effect on acid tolerance. The H90R iron-blind Fur protein also mediated acid shock induction of several Fur-dependent acid shock proteins and acid control of the hyd locus. In addition, a Fur superrepressor that constitutively repressed iron-regulated genes mediated normal Fur-dependent acid tolerance and pH-controlled gene expression. The results indicate the acid-sensing and iron-sensing mechanisms of Fur are separable by mutation and reinforce the concept of Fur as a major global regulator in the cell.


This article has been cited by other articles:

  • 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]  
  • Curtiss, R. III, Wanda, S.-Y., Gunn, B. M., Zhang, X., Tinge, S. A., Ananthnarayan, V., Mo, H., Wang, S., Kong, W. (2009). Salmonella enterica Serovar Typhimurium Strains with Regulated Delayed Attenuation In Vivo. Infect. Immun. 77: 1071-1082 [Abstract] [Full Text]  
  • Guillemet, M. L., Moreau, P. L. (2008). Fur-Dependent Detoxification of Organic Acids by rpoS Mutants during Prolonged Incubation under Aerobic, Phosphate Starvation Conditions. J. Bacteriol. 190: 5567-5575 [Abstract] [Full Text]  
  • Yuhara, S., Komatsu, H., Goto, H., Ohtsubo, Y., Nagata, Y., Tsuda, M. (2008). Pleiotropic roles of iron-responsive transcriptional regulator Fur in Burkholderia multivorans. Microbiology 154: 1763-1774 [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]  
  • Reid, A. N., Pandey, R., Palyada, K., Naikare, H., Stintzi, A. (2008). Identification of Campylobacter jejuni Genes Involved in the Response to Acidic pH and Stomach Transit. Appl. Environ. Microbiol. 74: 1583-1597 [Abstract] [Full Text]  
  • Reid, A. N., Pandey, R., Palyada, K., Whitworth, L., Doukhanine, E., Stintzi, A. (2008). Identification of Campylobacter jejuni Genes Contributing to Acid Adaptation by Transcriptional Profiling and Genome-Wide Mutagenesis. Appl. Environ. Microbiol. 74: 1598-1612 [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]  
  • Quatrini, R., Lefimil, C., Veloso, F. A., Pedroso, I., Holmes, D. S., Jedlicki, E. (2007). Bioinformatic prediction and experimental verification of Fur-regulated genes in the extreme acidophile Acidithiobacillus ferrooxidans. Nucleic Acids Res 35: 2153-2166 [Abstract] [Full Text]  
  • Maciag, A., Dainese, E., Rodriguez, G. M., Milano, A., Provvedi, R., Pasca, M. R., Smith, I., Palu, G., Riccardi, G., Manganelli, R. (2007). Global Analysis of the Mycobacterium tuberculosis Zur (FurB) Regulon. J. Bacteriol. 189: 730-740 [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]  
  • Bearson, S. M. D., Bearson, B. L., Rasmussen, M. A. (2006). Identification of Salmonella enterica Serovar Typhimurium Genes Important for Survival in the Swine Gastric Environment. Appl. Environ. Microbiol. 72: 2829-2836 [Abstract] [Full Text]  
  • Kim, J.-S., Sung, M.-H., Kho, D.-H., Lee, J. K. (2005). Induction of Manganese-Containing Superoxide Dismutase Is Required for Acid Tolerance in Vibrio vulnificus. J. Bacteriol. 187: 5984-5995 [Abstract] [Full Text]  
  • Quatrini, R., Lefimil, C., Holmes, D. S., Jedlicki, E. (2005). The ferric iron uptake regulator (Fur) from the extreme acidophile Acidithiobacillus ferrooxidans. Microbiology 151: 2005-2015 [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]  
  • Friedman, Y. E., O'Brian, M. R. (2004). The Ferric Uptake Regulator (Fur) Protein from Bradyrhizobium japonicum Is an Iron-responsive Transcriptional Repressor in Vitro. J. Biol. Chem. 279: 32100-32105 [Abstract] [Full Text]  
  • Friedman, Y. E., O'Brian, M. R. (2003). A Novel DNA-binding Site for the Ferric Uptake Regulator (Fur) Protein from Bradyrhizobium japonicum. J. Biol. Chem. 278: 38395-38401 [Abstract] [Full Text]  
  • Sala, C., Forti, F., Di Florio, E., Canneva, F., Milano, A., Riccardi, G., Ghisotti, D. (2003). Mycobacterium tuberculosis FurA Autoregulates Its Own Expression. J. Bacteriol. 185: 5357-5362 [Abstract] [Full Text]  
  • Seputiene, V., Motiejunas, D., Suziedelis, K., Tomenius, H., Normark, S., Melefors, O., Suziedeliene, E. (2003). Molecular Characterization of the Acid-Inducible asr Gene of Escherichia coli and Its Role in Acid Stress Response. J. Bacteriol. 185: 2475-2484 [Abstract] [Full Text]  
  • Wilson, J. W., Ramamurthy, R., Porwollik, S., McClelland, M., Hammond, T., Allen, P., Ott, C. M., Pierson, D. L., Nickerson, C. A. (2002). Microarray analysis identifies Salmonella genes belonging to the low-shear modeled microgravity regulon. Proc. Natl. Acad. Sci. USA 99: 13807-13812 [Abstract] [Full Text]  
  • Lewin, A. C., Doughty, P. A., Flegg, L., Moore, G. R., Spiro, S. (2002). The ferric uptake regulator of Pseudomonas aeruginosa has no essential cysteine residues and does not contain a structural zinc ion. Microbiology 148: 2449-2456 [Abstract] [Full Text]  
  • Sebastian, S., Agarwal, S., Murphy, J. R., Genco, C. A. (2002). The Gonococcal Fur Regulon: Identification of Additional Genes Involved in Major Catabolic, Recombination, and Secretory Pathways. J. Bacteriol. 184: 3965-3974 [Abstract] [Full Text]  
  • Campoy, S., Jara, M., Busquets, N., de Rozas, A. M. P., Badiola, I., Barbe, J. (2002). Intracellular cyclic AMP concentration is decreased in Salmonella typhimurium fur mutants. Microbiology 148: 1039-1048 [Abstract] [Full Text]  
  • Bijlsma, J. J. E., Waidner, B., Vliet, A. H. M. v., Hughes, N. J., Hag, S., Bereswill, S., Kelly, D. J., Vandenbroucke-Grauls, C. M. J. E., Kist, M., Kusters, J. G. (2002). The Helicobacter pylori Homologue of the Ferric Uptake Regulator Is Involved in Acid Resistance. Infect. Immun. 70: 606-611 [Abstract] [Full Text]  
  • Heimer, S. R., Welch, R. A., Perna, N. T., Posfai, G., Evans, P. S., Kaper, J. B., Blattner, F. R., Mobley, H. L. T. (2002). Urease of Enterohemorrhagic Escherichia coli: Evidence for Regulation by Fur and a trans-Acting Factor. Infect. Immun. 70: 1027-1031 [Abstract] [Full Text]  
  • Dubrac, S., Touati, D. (2002). Fur-mediated transcriptional and post-transcriptional regulation of FeSOD expression in Escherichia coli. Microbiology 148: 147-156 [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]  
  • Tsujibo, H., Miyamoto, K., Okamoto, T., Orikoshi, H., Inamori, Y. (2000). A Serine Protease-Encoding Gene (aprII) of Alteromonas sp. Strain O-7 Is Regulated by the Iron Uptake Regulator (Fur) Protein. Appl. Environ. Microbiol. 66: 3778-3783 [Abstract] [Full Text]  
  • Bang, I. S., Kim, B. H., Foster, J. W., Park, Y. K. (2000). OmpR Regulates the Stationary-Phase Acid Tolerance Response of Salmonella enterica Serovar Typhimurium. J. Bacteriol. 182: 2245-2252 [Abstract] [Full Text]  
  • Xiong, A., Singh, V. K., Cabrera, G., Jayaswal, R. K. (2000). Molecular characterization of the ferric-uptake regulator, Fur, from Staphylococcus aureus. Microbiology 146: 659-668 [Abstract] [Full Text]  
  • Escolar, L., Pérez-Martín, J., de Lorenzo, V. (1999). Opening the Iron Box: Transcriptional Metalloregulation by the Fur Protein. J. Bacteriol. 181: 6223-6229 [Full Text]  
  • Bsat, N., Helmann, J. D. (1999). Interaction of Bacillus subtilis Fur (Ferric Uptake Repressor) with the dhb Operator In Vitro and In Vivo. J. Bacteriol. 181: 4299-4307 [Abstract] [Full Text]  
  • Zhou, D., Hardt, W.-D., Galan, J. E. (1999). Salmonella typhimurium Encodes a Putative Iron Transport System within the Centisome 63 Pathogenicity Island. Infect. Immun. 67: 1974-1981 [Abstract] [Full Text]  
  • Heithoff, D. M., Conner, C. P., Hentschel, U., Govantes, F., Hanna, P. C., Mahan, M. J. (1999). Coordinate Intracellular Expression of Salmonella Genes Induced during Infection. J. Bacteriol. 181: 799-807 [Abstract] [Full Text]  
  • Park, K. R., Giard, J.-C., Eom, J. H., Bearson, S., Foster, J. W. (1999). Cyclic AMP Receptor Protein and TyrR Are Required for Acid pH and Anaerobic Induction of hyaB and aniC in Salmonella typhimurium. J. Bacteriol. 181: 689-694 [Abstract] [Full Text]  
  • Wong, H.-c., Peng, P.-Y., Han, J.-M., Chang, C.-Y., Lan, S.-L. (1998). Effect of Mild Acid Treatment on the Survival, Enteropathogenicity, and Protein Production in Vibrio parahaemolyticus. Infect. Immun. 66: 3066-3071 [Abstract] [Full Text]  
  • Bearson, B. L., Wilson, L., Foster, J. W. (1998). A Low pH-Inducible, PhoPQ-Dependent Acid Tolerance Response Protects Salmonella typhimurium against Inorganic Acid Stress. J. Bacteriol. 180: 2409-2417 [Abstract] [Full Text]  
  • Escolar, L., Pérez-Martín, J., de Lorenzo, V. (1998). Coordinated Repression In Vitro of the Divergent fepA-fes Promoters of Escherichia coli by the Iron Uptake Regulation (Fur) Protein. J. Bacteriol. 180: 2579-2582 [Abstract] [Full Text]  
  • Aldsworth, T. G., Sharman, R. L., Dodd, C. E. R., Stewart, G. S. A. B. (1998). A Competitive Microflora Increases the Resistance of Salmonella typhimurium to Inimical Processes: Evidence for a Suicide Response. Appl. Environ. Microbiol. 64: 1323-1327 [Abstract] [Full Text]  
  • Slauch, J, Taylor, R, Maloy, S (1997). Survival in a cruel world: how Vibrio cholerae and Salmonella respond to an unwilling host.. Genes Dev. 11: 1761-1774  
  • Escolar, L., Perez-Martin, J., de Lorenzo, V. (2000). Evidence of an Unusually Long Operator for the Fur Repressor in the Aerobactin Promoter of Escherichia coli. J. Biol. Chem. 275: 24709-24714 [Abstract] [Full Text]