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Latent Mycobacterium tuberculosis–persistence, patience, and winning by waiting

Nature Medicine volume 6, pages 1327–1329 (2000)Cite this article

Abstract

Mycobacterium tuberculosis is a globally successful pathogen due to its ability to persist for long periods of time unrecognized by the human immune system. The panoply of genes that allows the organism to enter latency and then re-emerge later during endogenous reinfection are now being elucidated. Novel antimicrobials and vaccines will need to target these mycobacterial pathogenic mechanisms to suceed against tuberculosis.

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References

  1. Medlar, E.M., Bernstein, S. & Steward, D.M. A bacteriologic study of resected tuberculous lesions. Am. Rev. Tuberc. 66, 36–43 (1952).

    CAS  PubMed  Google Scholar 

  2. Hobby, G.L. et al. The late emergence of M. tuberculosis in liquid cultures of pulmonary lesions resected from humans. Am. Rev. Tuberc. 70, 191–218 (1954).

    CAS  PubMed  Google Scholar 

  3. Opie, E.L. & Aronson, J.D. Tubercle bacilli in latent tuberculous lesions and in lung tissue without tuberculous lesions. Arch. Pathol. Lab. Med. 4, 1–21 (1927).

    Google Scholar 

  4. Comstock, G.W., Baum, C. & Snider, D.E., Jr. Isoniazid prophylaxis among Alaskan Eskimos: a final report of the bethel isoniazid studies. Am. Rev. Respir. Dis. 119, 827–830 (1972).

    Google Scholar 

  5. Cole, S.T. et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393, 537–544 (1998); erratum: 396, 190 (1998).

    Article  CAS  Google Scholar 

  6. DeMaio, J. et al. A stationary-phase stress-response σ factor from M. tuberculosis. Proc. Natl. Acad. Sci. USA. 93, 2790–2794 (1996).

    Article  CAS  Google Scholar 

  7. Chen, P. et al. Construction and characterization of a mycobacterium tuberculosis mutant lacking the alternate sigma factor gene, sigF. Infect. Immun. 68, 5575–80 (2000).

    Article  CAS  Google Scholar 

  8. Chen, P., Gomez, J. & Bishai, W.R. in Mycobacterial Transcription Regulation in Stationary Phase, in Molecular Genetics of Mycobacteria (eds. Hatfull, G.H & Jacobs, W.R.) 149–156 (ASM Press, Washington DC, 2000).

    Google Scholar 

  9. McCune, R.M. et al. Microbial Persistence II. Characteristics of the sterile state of tubercle bacilli. J. Exp. Med. 123, 469–486 (1966).

    Article  CAS  Google Scholar 

  10. McCune, R.M. et al. Microbial Persistence I. The capacity of tubercle bacilli to survive sterilization in mouse tissues. J. Exp. Med. 123, 445–468 (1966).

    Article  CAS  Google Scholar 

  11. Scanga, C.A. et al. Reactivation of latent tuberculosis: variations on the Cornell murine model. Infect. Immun. 67, 4531–4538 (1999).

    CAS  PubMed  Google Scholar 

  12. Miyazaki, E., Chaisson, R.E. & Bishai, W.R. Analysis of rifapentine for preventive therapy in the Cornell mouse model of latent tuberculosis. Antimicrob. Agents Chemother. 43, 2126–2130 (1999).

    Article  CAS  Google Scholar 

  13. Wayne, L.G. Synchronized replication of Mycobacterium tuberculosis. Infect. Immun. 17, 528–530 (1977).

    CAS  PubMed  Google Scholar 

  14. Wayne, L.G. & Lin, K.Y. Glyoxylate metabolism and adaptation of M. tuberculosis to survival under anaerobic conditions. Infect. Immun. 37, 1042–1049 (1982).

    CAS  PubMed  Google Scholar 

  15. Wayne, L.G. & Hayes, L.G. An in vitro model for sequential study of shiftdown of M. tuberculosis through two stages of nonreplicating persistence. Infect. Immun. 64, 2062–2069 (1996).

    CAS  PubMed  Google Scholar 

  16. Wayne, L.G. Dormancy of Mycobacterium tuberculosis and latency of disease. Eur. J. Clin. Microbiol. Infect. Dis. 13, 908–914 (1994).

    Article  CAS  Google Scholar 

  17. McKinney, J.D. et al. Persistence of M. tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 406, 735–738 (2000).

    Article  CAS  Google Scholar 

  18. Glickman, M.S., Cox, J.S. & Jacobs, W.R., Jr. A novel mycolic acid cyclopropane synthetase is required for coding, persistence, and virulence of M. tuberculosis. Mol. Cell 5, 717–727 (2000).

    Article  CAS  Google Scholar 

  19. Ramakrishnan, L., Federspiel, N.A. & Falkow, S. Granuloma-specific expression of mycobacterium virulence proteins from the glycine-rich PE-PGRS family. Science 288, 1436–1439 (2000).

    Article  CAS  Google Scholar 

  20. Wayne, L.G. & Sramek, H.A. Metronidazole is bactericidal to dormant cells of Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 38, 2054–2058 (1994).

    Article  CAS  Google Scholar 

  21. Dhillon, J. et al. Metronidazole has no antibacterial effect in Cornell model murine tuberculosis. Int. J. Tuberc. Lung Dis. 2, 736–742 (1998).

    CAS  PubMed  Google Scholar 

  22. Stead, W.W. Pathogenesis of a first episode of chronic pulmonary tuberculosis in man: recrudescence of residuals of the primary infection or exogenous reinfection? Am. Rev. Respir. Dis. 95, 729–745 (1967).

    CAS  PubMed  Google Scholar 

  23. Nardell, E. et al. Exogenous reinfection with tuberculosis in a shelter for the homeless. N. Engl. J. Med. 315, 1570–1575 (1996).

    Article  Google Scholar 

  24. Small, P.M. et al. Exogenous reinfection with multidrug-resistant M. tuberculosis in patients with advanced HIV infection. N. Engl. J. Med. 328, 1137–1144 (1993).

    Article  CAS  Google Scholar 

  25. van Rie, A. et al. Exogenous reinfection as a cause of recurrent tuberculosis after curative treatment. N. Engl. J. Med. 341, 1174–9 (1999).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Departments of Medicine and International Health, Johns Hopkins University, Baltimore, 21205, Maryland, USA

    Yukari C. Manabe & William R. Bishai

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  1. Yukari C. Manabe
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  2. William R. Bishai
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Manabe, Y., Bishai, W. Latent Mycobacterium tuberculosis–persistence, patience, and winning by waiting. Nat Med 6, 1327–1329 (2000). https://doi.org/10.1038/82139

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