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 Takaya, A.
Right arrow Articles by Yamamoto, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Takaya, A.
Right arrow Articles by Yamamoto, T.

 Previous Article  |  Next Article 

Infection and Immunity, March 2004, p. 1364-1373, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1364-1373.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The DnaK/DnaJ Chaperone Machinery of Salmonella enterica Serovar Typhimurium Is Essential for Invasion of Epithelial Cells and Survival within Macrophages, Leading to Systemic Infection

Akiko Takaya,1 Toshifumi Tomoyasu,1 Hidenori Matsui,2 and Tomoko Yamamoto1*

Department of Microbiology and Molecular Genetics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522,1 Department of Infection Control and Immunology, Kitasato Institute for Life Sciences, Kitasato University, Tokyo 108-8641, Japan2

Received 13 July 2003/ Returned for modification 17 September 2003/ Accepted 12 November 2003

Salmonella enterica serovar Typhimurium, similar to various facultative intracellular pathogens, has been shown to respond to the hostile conditions inside macrophages of the host organism by inducing stress proteins, such as DnaK. DnaK forms a chaperone machinery with the cochaperones DnaJ and GrpE. To elucidate the role of the DnaK chaperone machinery in the pathogenesis of S. enterica serovar Typhimurium, we first constructed an insertional mutation in the dnaK-dnaJ operon of pathogenic strain {chi}3306. The DnaK/DnaJ-depleted mutant was temperature sensitive for growth, that is, nonviable above 39°C. We then isolated a spontaneously occurring revertant of the dnaK-dnaJ-disrupted mutant at 39°C and used it for infection of mice. The mutant lost the ability to cause a lethal systemic disease in mice. The impaired ability for virulence was restored when a functional copy of the dnaK-dnaJ operon was provided, suggesting that the DnaK/DnaJ chaperone machinery is required by Salmonella for the systemic infection of mice. This result also indicates that with respect to the DnaK/DnaJ chaperone machinery, the cellular requirements for growth at a high temperature are not identical to the cellular requirements for the pathogenesis of Salmonella. Macrophage survival assays revealed that the DnaK/DnaJ-depleted mutant could not survive or proliferate at all within macrophages. Of further interest are the findings that the mutant could neither invade cultured epithelial cells nor secrete any of the invasion proteins encoded within Salmonella pathogenicity island 1. This is the first time that the DnaK/DnaJ chaperone machinery has been shown to be involved in bacterial invasion of epithelial cells.

* Corresponding author. Mailing address: Department of Microbiology and Molecular Genetics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522, Japan. Phone: 81-43-290-2928. Fax: 81-43-290-2929. E-mail: tomoko-y{at}p.chiba-u.ac.jp.

Editor: B. B. Finlay

Infection and Immunity, March 2004, p. 1364-1373, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1364-1373.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Matsui, M., Takaya, A., Yamamoto, T. (2008). {sigma}32-Mediated Negative Regulation of Salmonella Pathogenicity Island 1 Expression. J. Bacteriol. 190: 6636-6645 [Abstract] [Full Text]  
  • Menashe, O., Kaganskaya, E., Baasov, T., Yaron, S. (2008). Aminoglycosides Affect Intracellular Salmonella enterica Serovars Typhimurium and Virchow. Antimicrob. Agents Chemother. 52: 920-926 [Abstract] [Full Text]  
  • Tu, L. N., Jeong, H.-Y., Kwon, H.-Y., Ogunniyi, A. D., Paton, J. C., Pyo, S.-N., Rhee, D.-K. (2007). Modulation of Adherence, Invasion, and Tumor Necrosis Factor Alpha Secretion during the Early Stages of Infection by Streptococcus pneumoniae ClpL. Infect. Immun. 75: 2996-3005 [Abstract] [Full Text]  
  • Liebscher, M., Jahreis, G., Lucke, C., Grabley, S., Raina, S., Schiene-Fischer, C. (2007). Fatty Acyl Benzamido Antibacterials Based on Inhibition of DnaK-catalyzed Protein Folding. J. Biol. Chem. 282: 4437-4446 [Abstract] [Full Text]  
  • Shi, L., Adkins, J. N., Coleman, J. R., Schepmoes, A. A., Dohnkova, A., Mottaz, H. M., Norbeck, A. D., Purvine, S. O., Manes, N. P., Smallwood, H. S., Wang, H., Forbes, J., Gros, P., Uzzau, S., Rodland, K. D., Heffron, F., Smith, R. D., Squier, T. C. (2006). Proteomic Analysis of Salmonella enterica Serovar Typhimurium Isolated from RAW 264.7 Macrophages: IDENTIFICATION OF A NOVEL PROTEIN THAT CONTRIBUTES TO THE REPLICATION OF SEROVAR TYPHIMURIUM INSIDE MACROPHAGES. J. Biol. Chem. 281: 29131-29140 [Abstract] [Full Text]  
  • Henderson, B., Allan, E., Coates, A. R. M. (2006). Stress Wars: the Direct Role of Host and Bacterial Molecular Chaperones in Bacterial Infection. Infect. Immun. 74: 3693-3706 [Full Text]  
  • Chitlaru, T., Gat, O., Gozlan, Y., Ariel, N., Shafferman, A. (2006). Differential Proteomic Analysis of the Bacillus anthracis Secretome: Distinct Plasmid and Chromosome CO2-Dependent Cross Talk Mechanisms Modulate Extracellular Proteolytic Activities.. J. Bacteriol. 188: 3551-3571 [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»