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 Manca, C.
Right arrow Articles by Kaplan, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Manca, C.
Right arrow Articles by Kaplan, G.

 Previous Article  |  Next Article 

Infection and Immunity, January 1999, p. 74-79, Vol. 67, No. 1
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Mycobacterium tuberculosis Catalase and Peroxidase Activities and Resistance to Oxidative Killing in Human Monocytes In Vitro

Claudia Manca,1 Simon Paul,1 Clifton E. Barry III,2 Victoria H. Freedman,1 and Gilla Kaplan1,*

Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021,1 and Tuberculosis Research Unit, Laboratory of Intracellular Parasites, Rocky Mountain Laboratory, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 598402

Received 14 May 1998/Returned for modification 20 July 1998/Accepted 15 October 1998

Mycobacterium tuberculosis has a relatively high resistance to killing by hydrogen peroxide and organic peroxides. Resistance may be mediated by mycobacterial catalase-peroxidase (KatG) and possibly by alkyl hydroperoxide reductase (AhpC). To determine the interrelationship between sensitivity to H2O2, catalase and peroxidase activities, and bacillary growth rates measured both intracellularly in human monocytes and in culture medium, we examined one laboratory strain, two clinical isolates, and three recombinant strains of M. tuberculosis with differing levels of KatG and AhpC. Five of the mycobacterial strains had intracellular doubling times of 27 to 32 h, while one KatG-deficient clinical isolate (ATCC 35825) doubled in ~76 h. Killing of mycobacteria by exogenously added H2O2 was more pronounced for intracellular bacilli than for those bacilli derived from disrupted monocytes. Strains with no detectable KatG expression or catalase activity were relatively sensitive to killing (43 to 67% killing) by exogenous H2O2. However, once even minimal catalase activity was present, mycobacterial catalase activity over a 10-fold range (0.56 to 6.2 U/mg) was associated with survival of 85% of the bacilli. Peroxidase activity levels correlated significantly with resistance of the mycobacterial strains to H2O2-mediated killing. An endogenous oxidative burst induction by 4beta -phorbol 12beta -myristate 13alpha -acetate treatment of infected monocytes reduced the viability of the KatG null strain (H37Rv Inhr) but not the KatG-overexpressing strain [H37Rv(pMH59)]. These results suggest that mycobacterial resistance to oxidative metabolites (including H2O2 and other peroxides) may be an important mechanism of bacillary survival within the host phagocyte.

* Corresponding author. Mailing address: Laboratory of Cellular Physiology & Immunology, The Rockefeller University, 1230 York Ave., New York, NY 10021. Phone: (212) 327-8375. Fax: (212) 327-8875. E-mail: kaplang{at}rockvax.rockefeller.edu.

Infection and Immunity, January 1999, p. 74-79, Vol. 67, No. 1
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Bergval, I. L., Schuitema, A. R. J., Klatser, P. R., Anthony, R. M. (2009). Resistant mutants of Mycobacterium tuberculosis selected in vitro do not reflect the in vivo mechanism of isoniazid resistance. J Antimicrob Chemother 64: 515-523 [Abstract] [Full Text]  
  • Reich-Slotky, R., Kabbash, C. A., Della-Latta, P., Blanchard, J. S., Feinmark, S. J., Freeman, S., Kaplan, G., Shuman, H. A., Silverstein, S. C. (2009). Gemfibrozil Inhibits Legionella pneumophila and Mycobacterium tuberculosis Enoyl Coenzyme A Reductases and Blocks Intracellular Growth of These Bacteria in Macrophages. J. Bacteriol. 191: 5262-5271 [Abstract] [Full Text]  
  • Martinez-Pulgarin, S., Dominguez-Bernal, G., Orden, J. A., de la Fuente, R. (2009). Simultaneous lack of catalase and beta-toxin in Staphylococcus aureus leads to increased intracellular survival in macrophages and epithelial cells and to attenuated virulence in murine and ovine models. Microbiology 155: 1505-1515 [Abstract] [Full Text]  
  • Colangeli, R., Haq, A., Arcus, V. L., Summers, E., Magliozzo, R. S., McBride, A., Mitra, A. K., Radjainia, M., Khajo, A., Jacobs, W. R. Jr., Salgame, P., Alland, D. (2009). The multifunctional histone-like protein Lsr2 protects mycobacteria against reactive oxygen intermediates. Proc. Natl. Acad. Sci. USA 106: 4414-4418 [Abstract] [Full Text]  
  • Kurtz, S., McKinnon, K. P., Runge, M. S., Ting, J. P.-Y., Braunstein, M. (2006). The SecA2 Secretion Factor of Mycobacterium tuberculosis Promotes Growth in Macrophages and Inhibits the Host Immune Response. Infect. Immun. 74: 6855-6864 [Abstract] [Full Text]  
  • Daniel, D. S., Dai, G., Singh, C. R., Lindsey, D. R., Smith, A. K., Dhandayuthapani, S., Hunter, R. L. Jr, Jagannath, C. (2006). The Reduced Bactericidal Function of Complement C5-Deficient Murine Macrophages Is Associated with Defects in the Synthesis and Delivery of Reactive Oxygen Radicals to Mycobacterial Phagosomes. J. Immunol. 177: 4688-4698 [Abstract] [Full Text]  
  • Giles, S. S., Stajich, J. E., Nichols, C., Gerrald, Q. D., Alspaugh, J. A., Dietrich, F., Perfect, J. R. (2006). The Cryptococcus neoformans Catalase Gene Family and Its Role in Antioxidant Defense.. Eukaryot Cell 5: 1447-1459 [Abstract] [Full Text]  
  • Warner, D. F., Mizrahi, V. (2006). Tuberculosis Chemotherapy: the Influence of Bacillary Stress and Damage Response Pathways on Drug Efficacy. Clin. Microbiol. Rev. 19: 558-570 [Abstract] [Full Text]  
  • Sinha, A., Singh, A., Satchidanandam, V., Natarajan, K. (2006). Impaired Generation of Reactive Oxygen Species during Differentiation of Dendritic Cells (DCs) by Mycobacterium tuberculosis Secretory Antigen (MTSA) and Subsequent Activation of MTSA-DCs by Mycobacteria Results in Increased Intracellular Survival. J. Immunol. 177: 468-478 [Abstract] [Full Text]  
  • Guimaraes, B. G., Souchon, H., Honore, N., Saint-Joanis, B., Brosch, R., Shepard, W., Cole, S. T., Alzari, P. M. (2005). Structure and Mechanism of the Alkyl Hydroperoxidase AhpC, a Key Element of the Mycobacterium tuberculosis Defense System against Oxidative Stress. J. Biol. Chem. 280: 25735-25742 [Abstract] [Full Text]  
  • O'Sullivan, D. M., McHugh, T. D., Gillespie, S. H. (2005). Analysis of rpoB and pncA mutations in the published literature: an insight into the role of oxidative stress in Mycobacterium tuberculosis evolution?. J Antimicrob Chemother 55: 674-679 [Abstract] [Full Text]  
  • Song, Z., Marzilli, L., Greenlee, B. M., Chen, E. S., Silver, R. F., Askin, F. B., Teirstein, A. S., Zhang, Y., Cotter, R. J., Moller, D. R. (2005). Mycobacterial catalase-peroxidase is a tissue antigen and target of the adaptive immune response in systemic sarcoidosis. JEM 201: 755-767 [Abstract] [Full Text]  
  • Sano, K., Tomioka, H., Sato, K., Sano, C., Kawauchi, H., Cai, S., Shimizu, T. (2004). Interaction of Antimycobacterial Drugs with the Anti-Mycobacterium avium Complex Effects of Antimicrobial Effectors, Reactive Oxygen Intermediates, Reactive Nitrogen Intermediates, and Free Fatty Acids Produced by Macrophages. Antimicrob. Agents Chemother. 48: 2132-2139 [Abstract] [Full Text]  
  • Douglas, T., Daniel, D. S., Parida, B. K., Jagannath, C., Dhandayuthapani, S. (2004). Methionine Sulfoxide Reductase A (MsrA) Deficiency Affects the Survival of Mycobacterium smegmatis within Macrophages. J. Bacteriol. 186: 3590-3598 [Abstract] [Full Text]  
  • Srinivasa Rao, P. S., Yamada, Y., Leung, K. Y. (2003). A major catalase (KatB) that is required for resistance to H2O2 and phagocyte-mediated killing in Edwardsiella tarda. Microbiology 149: 2635-2644 [Abstract] [Full Text]  
  • Paris, S., Wysong, D., Debeaupuis, J.-P., Shibuya, K., Philippe, B., Diamond, R. D., Latge, J.-P. (2003). Catalases of Aspergillus fumigatus. Infect. Immun. 71: 3551-3562 [Abstract] [Full Text]  
  • DeVito, J. A., Morris, S. (2003). Exploring the Structure and Function of the Mycobacterial KatG Protein Using trans-Dominant Mutants. Antimicrob. Agents Chemother. 47: 188-195 [Abstract] [Full Text]  
  • Master, S. S., Springer, B., Sander, P., Boettger, E. C., Deretic, V., Timmins, G. S. (2002). Oxidative stress response genes in Mycobacterium tuberculosis: role of ahpC in resistance to peroxynitrite and stage-specific survival in macrophages. Microbiology 148: 3139-3144 [Abstract] [Full Text]  
  • Gomes, M. S., Appelberg, R. (2002). NRAMP1- or cytokine-induced bacteriostasis of Mycobacterium avium by mouse macrophages is independent of the respiratory burst. Microbiology 148: 3155-3160 [Abstract] [Full Text]  
  • Pym, A. S., Saint-Joanis, B., Cole, S. T. (2002). Effect of katG Mutations on the Virulence of Mycobacterium tuberculosis and the Implication for Transmission in Humans. Infect. Immun. 70: 4955-4960 [Abstract] [Full Text]  
  • Firmani, M. A., Riley, L. W. (2002). Reactive Nitrogen Intermediates Have a Bacteriostatic Effect on Mycobacterium tuberculosis In Vitro. J. Clin. Microbiol. 40: 3162-3166 [Abstract] [Full Text]  
  • Firmani, M. A., Riley, L. W. (2002). Mycobacterium tuberculosis CDC1551 Is Resistant to Reactive Nitrogen and Oxygen Intermediates In Vitro. Infect. Immun. 70: 3965-3968 [Abstract] [Full Text]  
  • Kaushal, D., Schroeder, B. G., Tyagi, S., Yoshimatsu, T., Scott, C., Ko, C., Carpenter, L., Mehrotra, J., Manabe, Y. C., Fleischmann, R. D., Bishai, W. R. (2002). Reduced immunopathology and mortality despite tissue persistence in a Mycobacterium tuberculosis mutant lacking alternative sigma factor, SigH. Proc. Natl. Acad. Sci. USA 99: 8330-8335 [Abstract] [Full Text]  
  • Nunn, C. M., Djordjevic, S., Hillas, P. J., Nishida, C. R., Ortiz de Montellano, P. R. (2002). The Crystal Structure of Mycobacterium tuberculosis Alkylhydroperoxidase AhpD, a Potential Target for Antitubercular Drug Design. J. Biol. Chem. 277: 20033-20040 [Abstract] [Full Text]  
  • Ahmed, H. J., Johansson, C., Svensson, L. A., Ahlman, K., Verdrengh, M., Lagergard, T. (2002). In Vitro and In Vivo Interactions of Haemophilusducreyi with Host Phagocytes. Infect. Immun. 70: 899-908 [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]  
  • Raman, S., Song, T., Puyang, X., Bardarov, S., Jacobs, W. R. Jr., Husson, R. N. (2001). The Alternative Sigma Factor SigH Regulates Major Components of Oxidative and Heat Stress Responses in Mycobacterium tuberculosis. J. Bacteriol. 183: 6119-6125 [Abstract] [Full Text]  
  • Fairbairn, I. P., Stober, C. B., Kumararatne, D. S., Lammas, D. A. (2001). ATP-Mediated Killing of Intracellular Mycobacteria by Macrophages Is a P2X7-Dependent Process Inducing Bacterial Death by Phagosome-Lysosome Fusion. J. Immunol. 167: 3300-3307 [Abstract] [Full Text]  
  • Piddington, D. L., Fang, F. C., Laessig, T., Cooper, A. M., Orme, I. M., Buchmeier, N. A. (2001). Cu,Zn Superoxide Dismutase of Mycobacterium tuberculosis Contributes to Survival in Activated Macrophages That Are Generating an Oxidative Burst. Infect. Immun. 69: 4980-4987 [Abstract] [Full Text]  
  • Harris, N. B., Barletta, R. G. (2001). Mycobacterium avium subsp. paratuberculosis in Veterinary Medicine. Clin. Microbiol. Rev. 14: 489-512 [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]  
  • Lefebre, M. D., Valvano, M. A. (2001). In vitro resistance of Burkholderia cepacia complex isolates to reactive oxygen species in relation to catalase and superoxide dismutase production. Microbiology 147: 97-109 [Abstract] [Full Text]  
  • Couture, M., Yeh, S.-R., Wittenberg, B. A., Wittenberg, J. B., Ouellet, Y., Rousseau, D. L., Guertin, M. (1999). A cooperative oxygen-binding hemoglobin from Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 96: 11223-11228 [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»