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. 1995 Sep;63(9):3428–3437. doi: 10.1128/iai.63.9.3428-3437.1995

Virulence ranking of some Mycobacterium tuberculosis and Mycobacterium bovis strains according to their ability to multiply in the lungs, induce lung pathology, and cause mortality in mice.

P L Dunn 1, R J North 1
PMCID: PMC173472  PMID: 7642273

Abstract

Three virulent strains of Mycobacterium tuberculosis (H37Rv, Erdman, and NYH-27) and two virulent strains of M. bovis (Ravenel and Branch) were compared in terms of their growth rates in the livers and the lungs of mice, their ability to cause lung pathology, and the time taken for them to cause death. In immunocompetent mice, all strains caused an infection that progressed for 20 days or more and then underwent resolution in the liver but not in the lungs. In the lungs, infection persisted and induced progressive pathology. According to host survival time, Ravenel was the most virulent strain, followed, in decreasing order of virulence, by Branch, H37Rv, Erdman, and NYH-27. The much longer survival times of mice infected with M. tuberculosis strains allowed time for lung histopathology to change from a histiocytic alveolitis to a chronic fibroblastic fibrosis that eventually obliterated most of the lung architecture. By contrast, in mice infected with M. bovis strains, the alveolitis that developed during early infection was rapid and expansive enough to cause death before chronic lung pathology became evident. In mice depleted of CD4+ T cells, increased growth of all virulent strains induced necrotic exudative lung lesions that rapidly filled most of the alveolar sacs with inflammatory cells. These mice died much earlier than infected control mice did. Attenuated strains had longer population doubling times in vivo and failed to cause progressive disease or pathology in the lungs or livers of immunocompetent mice.

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Selected References

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  1. Chatterjee D., Roberts A. D., Lowell K., Brennan P. J., Orme I. M. Structural basis of capacity of lipoarabinomannan to induce secretion of tumor necrosis factor. Infect Immun. 1992 Mar;60(3):1249–1253. doi: 10.1128/iai.60.3.1249-1253.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Collins F. M., Smith M. M. A comparative study of the virulence of mycobacterium tuberculosis measured in mice and guinea pigs. Am Rev Respir Dis. 1969 Nov;100(5):631–639. doi: 10.1164/arrd.1969.100.5.631. [DOI] [PubMed] [Google Scholar]
  3. Dunn P. L., North R. J. Selective radiation resistance of immunologically induced T cells as the basis for irradiation-induced T-cell-mediated regression of immunogenic tumor. J Leukoc Biol. 1991 Apr;49(4):388–396. doi: 10.1002/jlb.49.4.388. [DOI] [PubMed] [Google Scholar]
  4. Ellis R. C., Zabrowarny L. A. Safer staining method for acid fast bacilli. J Clin Pathol. 1993 Jun;46(6):559–560. doi: 10.1136/jcp.46.6.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hill A. R., Premkumar S., Brustein S., Vaidya K., Powell S., Li P. W., Suster B. Disseminated tuberculosis in the acquired immunodeficiency syndrome era. Am Rev Respir Dis. 1991 Nov;144(5):1164–1170. doi: 10.1164/ajrccm/144.5.1164. [DOI] [PubMed] [Google Scholar]
  6. Izzo A. A., North R. J. Evidence for an alpha/beta T cell-independent mechanism of resistance to mycobacteria. Bacillus-Calmette-Guerin causes progressive infection in severe combined immunodeficient mice, but not in nude mice or in mice depleted of CD4+ and CD8+ T cells. J Exp Med. 1992 Aug 1;176(2):581–586. doi: 10.1084/jem.176.2.581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Jacobs W. R., Jr Advances in mycobacterial genetics: new promises for old diseases. Immunobiology. 1992 Feb;184(2-3):147–156. doi: 10.1016/S0171-2985(11)80472-9. [DOI] [PubMed] [Google Scholar]
  8. MACKANESS G. B., SMITH N., WELLS A. Q. The growth of intracellular tubercle bacilli in relation to their virulence. Am Rev Tuberc. 1954 Apr;69(4):479–494. doi: 10.1164/art.1954.69.4.479. [DOI] [PubMed] [Google Scholar]
  9. MITCHISON D. A., BHATIA A. L., RADHAKRISHNA S., SELKON J. B., SUBBAIAH T. V., WALLACE J. G. The virulence in the guinea-pig of tubercle bacilli isolated before treatment from South Indian patients with pulmonary tuberculosis. I. Homogeneity of the investigation and a critique of the virulence test. Bull World Health Organ. 1961;25:285–312. [PMC free article] [PubMed] [Google Scholar]
  10. Moreno C., Taverne J., Mehlert A., Bate C. A., Brealey R. J., Meager A., Rook G. A., Playfair J. H. Lipoarabinomannan from Mycobacterium tuberculosis induces the production of tumour necrosis factor from human and murine macrophages. Clin Exp Immunol. 1989 May;76(2):240–245. [PMC free article] [PubMed] [Google Scholar]
  11. North R. J., Izzo A. A. Mycobacterial virulence. Virulent strains of Mycobacteria tuberculosis have faster in vivo doubling times and are better equipped to resist growth-inhibiting functions of macrophages in the presence and absence of specific immunity. J Exp Med. 1993 Jun 1;177(6):1723–1733. doi: 10.1084/jem.177.6.1723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. PIERCE C. H., DUBOS R. J., SCHAEFER W. B. Multiplication and survival of tubercle bacilli in the organs of mice. J Exp Med. 1953 Feb 1;97(2):189–206. doi: 10.1084/jem.97.2.189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Pascopella L., Collins F. M., Martin J. M., Lee M. H., Hatfull G. F., Stover C. K., Bloom B. R., Jacobs W. R., Jr Use of in vivo complementation in Mycobacterium tuberculosis to identify a genomic fragment associated with virulence. Infect Immun. 1994 Apr;62(4):1313–1319. doi: 10.1128/iai.62.4.1313-1319.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Restrepo S., Tobon A., Trujillo J., Restrepo A. Development of pulmonary fibrosis in mice during infection with Paracoccidioides brasiliensis conidia. J Med Vet Mycol. 1992;30(3):173–184. [PubMed] [Google Scholar]
  15. Roach T. I., Barton C. H., Chatterjee D., Blackwell J. M. Macrophage activation: lipoarabinomannan from avirulent and virulent strains of Mycobacterium tuberculosis differentially induces the early genes c-fos, KC, JE, and tumor necrosis factor-alpha. J Immunol. 1993 Mar 1;150(5):1886–1896. [PubMed] [Google Scholar]
  16. SWEDBERG B. Studies in experimental tuberculosis; an investigation of some problems of immunity and resistance. Acta Med Scand Suppl. 1951;254:1–120. [PubMed] [Google Scholar]
  17. Salizzoni J. L., Tiruviluamala P., Reichman L. B. Liver transplantation: an unheralded probable risk for tuberculosis. Tuber Lung Dis. 1992 Aug;73(4):232–238. doi: 10.1016/0962-8479(92)90092-X. [DOI] [PubMed] [Google Scholar]
  18. Stover C. K., de la Cruz V. F., Fuerst T. R., Burlein J. E., Benson L. A., Bennett L. T., Bansal G. P., Young J. F., Lee M. H., Hatfull G. F. New use of BCG for recombinant vaccines. Nature. 1991 Jun 6;351(6326):456–460. doi: 10.1038/351456a0. [DOI] [PubMed] [Google Scholar]
  19. Travis W. D., Lack E. E., Ognibene F. P., Suffredini A. F., Shelhamer J. Lung biopsy interpretation in the acquired immunodeficiency syndrome: experience of the National Institutes of Health with literature review. Prog AIDS Pathol. 1989;1:51–84. [PubMed] [Google Scholar]

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