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 Zahrt, T. C.
Right arrow Articles by Deretic, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zahrt, T. C.
Right arrow Articles by Deretic, V.

 Previous Article  |  Next Article 

Journal of Bacteriology, July 2000, p. 3832-3838, Vol. 182, No. 13
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

An Essential Two-Component Signal Transduction System in Mycobacterium tuberculosis

Thomas C. Zahrt and Vojo Deretic*

Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0620

Received 4 January 2000/Accepted 30 March 2000

The bacterial two-component signal transduction systems regulate adaptation processes and are likely to play a role in Mycobacterium tuberculosis physiology and pathogenesis. The previous initial characterization of an M. tuberculosis response regulator from one of these systems, mtrA-mtrB, suggested its transcriptional activation during infection of phagocytic cells. In this work, we further characterized the mtrA response regulator from M. tuberculosis H37Rv. Inactivation of mtrA on the chromosome of M. tuberculosis H37Rv was possible only in the presence of plasmid-borne functional mtrA, suggesting that this response regulator is essential for M. tuberculosis viability. In keeping with these findings, expression of mtrA in M. tuberculosis H37Rv was detectable during in vitro growth, as determined by S1 nuclease protection and primer extension analyses of mRNA levels and mapping of transcript 5' ends. The mtrA gene was expressed differently in virulent M. tuberculosis and the vaccine strain M. tuberculosis var. bovis BCG during infection of macrophages, as determined by monitoring of mtrA-gfp fusion activity. In M. bovis BCG, mtrA was induced upon entry into macrophages. In M. tuberculosis H37Rv, its expression was constitutive and unchanged upon infection of murine or human monocyte-derived macrophages. In conclusion, these results identify mtrA as an essential response regulator gene in M. tuberculosis which is differentially expressed in virulent and avirulent strains during growth in macrophages.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Michigan Medical School, Medical Science Bldg. II, Ann Arbor, MI 48109-0620. Phone: (734) 763-1580. Fax: (734) 647-6243. E-mail: deretic{at}umich.edu.

Journal of Bacteriology, July 2000, p. 3832-3838, Vol. 182, No. 13
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Guo, M., Feng, H., Zhang, J., Wang, W., Wang, Y., Li, Y., Gao, C., Chen, H., Feng, Y., He, Z.-G. (2009). Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res 19: 1301-1308 [Abstract] [Full Text]  
  • Winkler, M. E., Hoch, J. A. (2008). Essentiality, Bypass, and Targeting of the YycFG (VicRK) Two-Component Regulatory System in Gram-Positive Bacteria. J. Bacteriol. 190: 2645-2648 [Full Text]  
  • Harriff, M. J., Wu, M., Kent, M. L., Bermudez, L. E. (2008). Species of Environmental Mycobacteria Differ in Their Abilities To Grow in Human, Mouse, and Carp Macrophages and with Regard to the Presence of Mycobacterial Virulence Genes, as Observed by DNA Microarray Hybridization. Appl. Environ. Microbiol. 74: 275-285 [Abstract] [Full Text]  
  • Moker, N., Reihlen, P., Kramer, R., Morbach, S. (2007). Osmosensing Properties of the Histidine Protein Kinase MtrB from Corynebacterium glutamicum. J. Biol. Chem. 282: 27666-27677 [Abstract] [Full Text]  
  • Talaat, A. M., Ward, S. K., Wu, C.-W., Rondon, E., Tavano, C., Bannantine, J. P., Lyons, R., Johnston, S. A. (2007). Mycobacterial Bacilli Are Metabolically Active during Chronic Tuberculosis in Murine Lungs: Insights from Genome-Wide Transcriptional Profiling. J. Bacteriol. 189: 4265-4274 [Abstract] [Full Text]  
  • Moker, N., Kramer, J., Unden, G., Kramer, R., Morbach, S. (2007). In Vitro Analysis of the Two-Component System MtrB-MtrA from Corynebacterium glutamicum. J. Bacteriol. 189: 3645-3649 [Abstract] [Full Text]  
  • Yukawa, H., Omumasaba, C. A., Nonaka, H., Kos, P., Okai, N., Suzuki, N., Suda, M., Tsuge, Y., Watanabe, J., Ikeda, Y., Vertes, A. A., Inui, M. (2007). Comparative analysis of the Corynebacterium glutamicum group and complete genome sequence of strain R. Microbiology 153: 1042-1058 [Abstract] [Full Text]  
  • Fernandez, P., Saint-Joanis, B., Barilone, N., Jackson, M., Gicquel, B., Cole, S. T., Alzari, P. M. (2006). The Ser/Thr Protein Kinase PknB Is Essential for Sustaining Mycobacterial Growth. J. Bacteriol. 188: 7778-7784 [Abstract] [Full Text]  
  • Hutchings, M. I., Hong, H.-J., Leibovitz, E., Sutcliffe, I. C., Buttner, M. J. (2006). The {sigma}E Cell Envelope Stress Response of Streptomyces coelicolor Is Influenced by a Novel Lipoprotein, CseA.. J. Bacteriol. 188: 7222-7229 [Abstract] [Full Text]  
  • Slayden, R. A., Knudson, D. L., Belisle, J. T. (2006). Identification of cell cycle regulators in Mycobacterium tuberculosis by inhibition of septum formation and global transcriptional analysis. Microbiology 152: 1789-1797 [Abstract] [Full Text]  
  • Pagan-Ramos, E., Master, S. S., Pritchett, C. L., Reimschuessel, R., Trucksis, M., Timmins, G. S., Deretic, V. (2006). Molecular and Physiological Effects of Mycobacterial oxyR Inactivation.. J. Bacteriol. 188: 2674-2680 [Abstract] [Full Text]  
  • Cangelosi, G. A., Do, J. S., Freeman, R., Bennett, J. G., Semret, M., Behr, M. A. (2006). The Two-Component Regulatory System mtrAB Is Required for Morphotypic Multidrug Resistance in Mycobacterium avium. Antimicrob. Agents Chemother. 50: 461-468 [Abstract] [Full Text]  
  • Wang, R., Prince, J. T., Marcotte, E. M. (2005). Mass spectrometry of the M. smegmatis proteome: Protein expression levels correlate with function, operons, and codon bias. Genome Res 15: 1118-1126 [Abstract] [Full Text]  
  • Carroll, P., Muttucumaru, D. G. N., Parish, T. (2005). Use of a Tetracycline-Inducible System for Conditional Expression in Mycobacterium tuberculosis and Mycobacterium smegmatis. Appl. Environ. Microbiol. 71: 3077-3084 [Abstract] [Full Text]  
  • Williams, T., Bauer, S., Beier, D., Kuhn, M. (2005). Construction and Characterization of Listeria monocytogenes Mutants with In-Frame Deletions in the Response Regulator Genes Identified in the Genome Sequence. Infect. Immun. 73: 3152-3159 [Abstract] [Full Text]  
  • Schar, J., Sickmann, A., Beier, D. (2005). Phosphorylation-Independent Activity of Atypical Response Regulators of Helicobacter pylori. J. Bacteriol. 187: 3100-3109 [Abstract] [Full Text]  
  • Thompson, C. R., Iyer, S. S., Melrose, N., VanOosten, R., Johnson, K., Pitson, S. M., Obeid, L. M., Kusner, D. J. (2005). Sphingosine Kinase 1 (SK1) Is Recruited to Nascent Phagosomes in Human Macrophages: Inhibition of SK1 Translocation by Mycobacterium tuberculosis. J. Immunol. 174: 3551-3561 [Abstract] [Full Text]  
  • He, H., Zahrt, T. C. (2005). Identification and Characterization of a Regulatory Sequence Recognized by Mycobacterium tuberculosis Persistence Regulator MprA. J. Bacteriol. 187: 202-212 [Abstract] [Full Text]  
  • Bent, C. J., Isaacs, N. W., Mitchell, T. J., Riboldi-Tunnicliffe, A. (2004). Crystal Structure of the Response Regulator 02 Receiver Domain, the Essential YycF Two-Component System of Streptococcus pneumoniae in both Complexed and Native States. J. Bacteriol. 186: 2872-2879 [Abstract] [Full Text]  
  • Ewann, F., Locht, C., Supply, P. (2004). Intracellular autoregulation of the Mycobacterium tuberculosis PrrA response regulator. Microbiology 150: 241-246 [Abstract] [Full Text]  
  • Zahrt, T. C., Wozniak, C., Jones, D., Trevett, A. (2003). Functional Analysis of the Mycobacterium tuberculosis MprAB Two-Component Signal Transduction System. Infect. Immun. 71: 6962-6970 [Abstract] [Full Text]  
  • Timm, J., Post, F. A., Bekker, L.-G., Walther, G. B., Wainwright, H. C., Manganelli, R., Chan, W.-T., Tsenova, L., Gold, B., Smith, I., Kaplan, G., McKinney, J. D. (2003). Differential expression of iron-, carbon-, and oxygen-responsive mycobacterial genes in the lungs of chronically infected mice and tuberculosis patients. Proc. Natl. Acad. Sci. USA 100: 14321-14326 [Abstract] [Full Text]  
  • Recchi, C., Sclavi, B., Rauzier, J., Gicquel, B., Reyrat, J.-M. (2003). Mycobacterium tuberculosis Rv1395 Is a Class III Transcriptional Regulator of the AraC Family Involved in Cytochrome P450 Regulation. J. Biol. Chem. 278: 33763-33773 [Abstract] [Full Text]  
  • Smith, I. (2003). Mycobacterium tuberculosis Pathogenesis and Molecular Determinants of Virulence. Clin. Microbiol. Rev. 16: 463-496 [Abstract] [Full Text]  
  • Parish, T., Smith, D. A., Kendall, S., Casali, N., Bancroft, G. J., Stoker, N. G. (2003). Deletion of Two-Component Regulatory Systems Increases the Virulence of Mycobacterium tuberculosis. Infect. Immun. 71: 1134-1140 [Abstract] [Full Text]  
  • Rodriguez, G. M., Voskuil, M. I., Gold, B., Schoolnik, G. K., Smith, I. (2002). ideR, an Essential Gene in Mycobacterium tuberculosis: Role of IdeR in Iron-Dependent Gene Expression, Iron Metabolism, and Oxidative Stress Response. Infect. Immun. 70: 3371-3381 [Abstract] [Full Text]  
  • Benoit, S., Benachour, A., Taouji, S., Auffray, Y., Hartke, A. (2002). H2O2, Which Causes Macrophage-Related Stress, Triggers Induction of Expression of Virulence-Associated Plasmid Determinants in Rhodococcus equi. Infect. Immun. 70: 3768-3776 [Abstract] [Full Text]  
  • Ewann, F., Jackson, M., Pethe, K., Cooper, A., Mielcarek, N., Ensergueix, D., Gicquel, B., Locht, C., Supply, P. (2002). Transient Requirement of the PrrA-PrrB Two-Component System for Early Intracellular Multiplication of Mycobacterium tuberculosis. Infect. Immun. 70: 2256-2263 [Abstract] [Full Text]  
  • Hobson, R. J., McBride, A. J. A., Kempsell, K. E., Dale, J. W. (2002). Use of an arrayed promoter-probe library for the identification of macrophage-regulated genes in Mycobacterium tuberculosis. Microbiology 148: 1571-1579 [Abstract] [Full Text]  
  • Haydel, S. E., Benjamin, W. H. Jr., Dunlap, N. E., Clark-Curtiss, J. E. (2002). Expression, Autoregulation, and DNA Binding Properties of the Mycobacterium tuberculosis TrcR Response Regulator. J. Bacteriol. 184: 2192-2203 [Abstract] [Full Text]  
  • Zahrt, T. C., Deretic, V. (2001). Mycobacterium tuberculosis signal transduction system required for persistent infections. Proc. Natl. Acad. Sci. USA 98: 12706-12711 [Abstract] [Full Text]  
  • Master, S., Zahrt, T. C., Song, J., Deretic, V. (2001). Mapping of Mycobacterium tuberculosis katG Promoters and Their Differential Expression in Infected Macrophages. J. Bacteriol. 183: 4033-4039 [Abstract] [Full Text]  
  • Singh, K. K., Zhang, X., Patibandla, A. S., Chien, P. Jr., Laal, S. (2001). Antigens of Mycobacterium tuberculosis Expressed during Preclinical Tuberculosis: Serological Immunodominance of Proteins with Repetitive Amino Acid Sequences. Infect. Immun. 69: 4185-4191 [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»