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Virulent clinical isolates of Mycobacterium tuberculosis grow rapidly and induce cellular necrosis but minimal apoptosis in murine macrophages
Abstract
In this study, we investigated the ability of four clinical isolates of Mycobacterium tuberculosis representing a range of virulence for their capacity to grow in bone marrow-derived macrophages. The rate of growth of each of the isolates in macrophages reflected their known virulence, but the most virulent isolates strongly induced production of the cytokine tumor necrosis factor α. A key difference, however, was the degree of cell cytotoxicity observed with the more virulent strains ater several days in culture. Staining of cell monolayers for DNA fragmentation indicative of apoptosis showed that this was minimal and only evident to any degree in macrophages infected with the most virulent strains. In contrast, electron microscopy revealed damage of macrophages consistent with cell necrosis. These results suggest that rapid intracellular growth rate and induction of necrotic cell death within host macrophages are virulence factors of M. tuberculosis in the early stages of bacterial infection. They further imply that infected cell apoptosis, regarded as a defense mechanism or cross-priming mechanism, plays a minimal role.
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“Certain virulent M. tuberculosis strains trigger necrosis by inner mitochondrial membrane rupture (124–127).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [127]
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Cites
Dye, C., Scheele, S., >Dolin, P., Pathania, V. S., Raviglione, M. C., & for the WHO Global Surveillance and Monitoring Project (1999) · JAMA · doi:10.1001/jama.282.7.677 · Cited by 2,955
The Growing Burden of Tuberculosis: Global Trends and Interactions With the HIV Epidemic
Corbett, E. L., Watt, C. J., Walker, N., Maher, D., Williams, B. G., Raviglione, M. C., & Dye, C. (2003) · Archives of Internal Medicine · doi:10.1001/archinte.163.9.1009 · Cited by 2,553
McKinney, J. D., zu Bentrup, K. H., Muñoz‐Elías, E. J., Miczák, A., Chen, B., Chan, W.-T., Swenson, D. L., Sacchettini, J. C., Jacobs, W. R., & Russell, D. G. (2000) · Nature · doi:10.1038/35021074 · Cited by 1,361
Mycobacterium tuberculosis Pathogenesis and Molecular Determinants of Virulence
Smith, I. (2003) · Clinical Microbiology Reviews · doi:10.1128/cmr.16.3.463-496.2003 · Cited by 1,154
Mycobacterium tuberculosis: here today, and here tomorrow
Russell, D. G. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35085034 · Cited by 796
Hsu, T., Hingley-Wilson, S. M., Chen, B., Chen, M., Dai, A. Z., Morin, P. M., Marks, C. B., Padiyar, J., Goulding, C., Gingery, M., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1635213100 · Cited by 731
Glickman, M. S., Cox, J. S., & Jacobs, W. R. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80250-6 · Cited by 656
Innate Immunity toMycobacterium tuberculosis
van Crevel, R., Ottenhoff, T. H. M., & van der Meer, J. W. M. (2002) · Clinical Microbiology Reviews · doi:10.1128/cmr.15.2.294-309.2002 · Cited by 602
Deletion of RD1 from Mycobacterium tuberculosis Mimics Bacille Calmette‐Guérin Attenuation
Lewis, K. N., Liao, R., Guinn, K. M., Hickey, M. J., Smith, S., Behr, M. A., & Sherman, D. R. (2003) · The Journal of Infectious Diseases · doi:10.1086/345862 · Cited by 588
Worldwide Occurrence of Beijing/W Strains ofMycobacterium tuberculosis: A Systematic Review
Glynn, J. R., Whiteley, J., Bifani, P. J., Kremer, K., & van Soolingen, D. (2002) · Emerging infectious diseases · doi:10.3201/eid0805.020002 · Cited by 576
Apoptosis facilitates antigen presentation to T lymphocytes through MHC-I and CD1 in tuberculosis
Schaible, U. E., Winau, F., Sieling, P. A., Fischer, K., Collins, H. L., Hagens, K., Modlin, R. L., Brinkmann, V., & Kaufmann, S. H. E. (2003) · Nature Medicine · doi:10.1038/nm906 · Cited by 546
Virulent Mycobacterium tuberculosis Strains Evade Apoptosis of Infected Alveolar Macrophages
Keane, J., Remold, H. G., & Kornfeld, H. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.4.2016 · Cited by 542
Guinn, K. M., Hickey, M. J., Mathur, S. K., Zakel, K. L., Grotzke, J. E., Lewinsohn, D. M., Smith, S., & Sherman, D. R. (2004) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03844.x · Cited by 508
Global dissemination of the Mycobacterium tuberculosis W-Beijing family strains
Bifani, P. J., Mathema, B., Kurepina, N. E., & Kreiswirth, B. N. (2002) · Trends in Microbiology · doi:10.1016/s0966-842x(01)02277-6 · Cited by 499
Ipr1 gene mediates innate immunity to tuberculosis
Pan, H., Yan, B., Rojas, M., Shebzukhov, Y. V., Zhou, H., Kobzik, L., Higgins, D. E., Daly, M. J., Bloom, B. R., & Kramnik, I. (2005) · Nature · doi:10.1038/nature03419 · Cited by 471
Mycobacterium tuberculosis Growth at theCavity Surface: a Microenvironment with FailedImmunity
Kaplan, G., Post, F. A., Moreira, A. L., Wainwright, H., Kreiswirth, B. N., Tanverdi, M., Mathema, B., Ramaswamy, S. V., Walther, G., Steyn, L. M., et al. (2003) · Infection and Immunity · doi:10.1128/iai.71.12.7099-7108.2003 · Cited by 344
Oxygenated mycolic acids are necessary for virulence of Mycobacterium tuberculosis in mice
Dubnau, E., Chan, J., Raynaud, C., Mohan, V. P., Lanéelle, M., Yu, K., Quémard, A., Smith, I., & Daffé, M. (2000) · Molecular Microbiology · doi:10.1046/j.1365-2958.2000.01882.x · Cited by 335
Immunopathology of tuberculosis: roles of macrophages and monocytes
Fenton, M. J., & Vermeulen, M. W. (1996) · Infection and Immunity · doi:10.1128/iai.64.3.683-690.1996 · Cited by 303
The chemical structure of the cord factor of Mycobacterium tuberculosis
Noll, H., Blöch, H., Asselineau, J., & LEDERER, E. (1956) · Biochimica et Biophysica Acta · doi:10.1016/0006-3002(56)90289-x · Cited by 298
Rhoades, E. R., Frank, A. A., & Orme, I. M. (1997) · Tubercle and Lung Disease · doi:10.1016/s0962-8479(97)90016-2 · Cited by 274
Self-citationSly, L. M., Hingley‐Wilson, S., Reiner, N. E., & McMaster, W. R. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.1.430 · Cited by 249
Rojas, M., Olivier, M., Gros, P., Barrera, L. F., & García, L. F. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.10.6122 · Cited by 213
Rojas, M., Olivier, M., Gros, P., Barrera, L. F., & García, L. F. (1999) · PubMed · Cited by 208
Danelishvili, L., McGarvey, J. A., Li, Y., & Bermudez, L. E. (2003) · Cellular Microbiology · doi:10.1046/j.1462-5822.2003.00312.x · Cited by 205
Ordway, D. J., Viveiros, M., Leandro, C., Bettencourt, R., Almeida, J. M. D. N., Martins, M., Kristiansen, J. E., Molnar, J. A., & Amaral, L. (2003) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.3.917-922.2003 · Cited by 201
Self-citationTurner, O. C., Basaraba, R. J., & Orme, I. M. (2003) · Infection and Immunity · doi:10.1128/iai.71.2.864-871.2003 · Cited by 168
Self-citationDunn, P., & North, R. J. (1995) · Infection and Immunity · doi:10.1128/iai.63.9.3428-3437.1995 · Cited by 164
North, R. J., & Izzo, A. A. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.177.6.1723 · Cited by 138
Indrigo, J., Hunter, R. L., & Actor, J. K. (2002) · Microbiology · doi:10.1099/00221287-148-7-1991 · Cited by 133
Silver, R. F., Li, Q., & Ellner, J. J. (1998) · Infection and Immunity · doi:10.1128/iai.66.3.1190-1199.1998 · Cited by 133
Drug-resistant strains of Mycobacterium tuberculosis exhibit a range of virulence for mice
Ordway, D. J., Sonnenberg, M. G., Donahue, S. A., Belisle, J. T., & Orme, I. M. (1995) · Infection and Immunity · doi:10.1128/iai.63.2.741-743.1995 · Cited by 120
Self-citationApoptosis and T Cell Hyporesponsiveness in Pulmonary Tuberculosis
Hirsch, C. S., Toossi, Z., Vanham, G. L., Johnson, J. L., Peters, P., Okwera, A., Mugerwa, R. D., Mugyenyi, P. N., & Ellner, J. J. (1999) · The Journal of Infectious Diseases · doi:10.1086/314667 · Cited by 118
Cegielski, J. P., Chin, D. P., Espinal, M., Frieden, T. R., Cruz, R. R., Talbot, E. A., Weil, D. E. C., Zaleskis, R., & Raviglione, M. C. (2002) · Infectious Disease Clinics of North America · doi:10.1016/s0891-5520(03)00045-x · Cited by 113
Hirsch, C. S., Toossi, Z., Johnson, J. L., Luzze, H., Ntambi, L., Peters, P., McHugh, M. J., Okwera, A., Joloba, M. L., Mugyenyi, P. N., et al. (2001) · The Journal of Infectious Diseases · doi:10.1086/318817 · Cited by 100
Wren, B. W., Stabler, R. A., DAS, S. S., Butcher, P. D., Mangan, J. A., Clarke, J. D., Casali, N., Parish, T., & Stoker, N. G. (1998) · Microbiology · doi:10.1099/00221287-144-5-1205 · Cited by 73
Dynamics and control of the global tuberculosis epidemic
Bleed, D. M., Dye, C., & Raviglione, M. C. (2000) · Current Opinion in Pulmonary Medicine · doi:10.1097/00063198-200005000-00002 · Cited by 62
Lasco, T. M., Turner, O. C., Cassone, L., Sugawara, I., Yamada, H., McMurray, D. N., & Orme, I. M. (2004) · Infection and Immunity · doi:10.1128/iai.72.2.1147-1149.2004 · Cited by 61
Self-citationBehling, C. A., Bennett, B. T., Takayama, K., & Hunter, R. L. (1993) · Infection and Immunity · doi:10.1128/iai.61.6.2296-2303.1993 · Cited by 50
Sarmento, A., & Appelberg, R. (1995) · Infection and Immunity · doi:10.1128/iai.63.10.3759-3764.1995 · Cited by 47
Mycobacterium tuberculosisBeijing Genotype1
Lillebæk, T., Andersen, Å. B., Dirksen, A., Glynn, J. R., & Kremer, K. (2003) · Emerging infectious diseases · doi:10.3201/eid0912.030276 · Cited by 46
Richardson, M., van Lill, S. W. P., van der Spuy, G. D., Münch, Z., Booysen, C. N., Beyers, N., van Helden, P. D., & Warren, R. M. (2002) · PubMed · Cited by 39
Granuloma Formation in Mouse and Guinea Pig Models of Experimental Tuberculosis
Turner, O. C., Basaraba, R. J., Frank, A. A., & Orme, I. M. (2014) · ASM Press eBooks · doi:10.1128/9781555817879.ch3 · Cited by 38
Self-citationSirakova, T. D., Fitzmaurice, A. M., & Kolattukudy, P. E. (2002) · Journal of Bacteriology · doi:10.1128/jb.184.24.6796-6802.2002 · Cited by 29
Rojas, M., Barrera, L. F., & García, L. F. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8802 · Cited by 26
Animal and cell-culture models for the study of mycobacterial infections and treatment
Orme, I. M., Roberts, A. D., Furney, S. K., & Skinner, P. S. (1994) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/bf02111500 · Cited by 22
Self-citationVirulence of recent notorious Mycobacterium tuberculosis isolates
Orme, I. M. (1999) · Tubercle and Lung Disease · doi:10.1054/tuld.1999.0221 · Cited by 17
Self-citationGrowth of recombinant Mycobacterium tuberculosis H37Ra in mouse macrophages
Falcone, V., & Collins, F. M. (1997) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.1997.4201314.x · Cited by 5
The role of cord factor in pathogenesis of tuberculosis.
Katô, M. (1971) · PubMed · Cited by 1
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Research works printed but not linked: 2
- Turner, 2003, Granulomatous Infections and Inflammation: Cellular and Molecular Mechanisms, 65
- Junqueira-Kipnis, 2005, Interferon independent pulmonary resistance to Mycobacterium bovis BCG in mice in the absence of necrosis
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Chen, M., Divangahi, M., Gan, H., Shin, D. S., Hong, S., Lee, D. M., Serhan, C. N., Behar, S. M., & Remold, H. G. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20080767 · Cited by 352
Kumar, D., Nath, L., Kamal, M. A., Varshney, A., Jain, A., Singh, S., & Rao, K. V. S. (2010) · Cell · doi:10.1016/j.cell.2010.02.012 · Cited by 347
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Herbst, S., Schaible, U. E., & Schneider, B. E. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019105 · Cited by 277
Homolka, S., Niemann, S., Russell, D. G., & Rohde, K. H. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000988 · Cited by 250
Metadata
- Authors
- Park, J. S., Tamayo, M. H., Gonzalez-Juarrero, M., Orme, I. M., & Ordway, D. J.
- Affiliations
- Colorado State University (US)
- Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University , Fort Collins
- Corresponding author
- Orme, Ian M
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-11-07
- Volume
- 79
- Issue
- 1
- Pages
- 80-86
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- OpenAlex
- W2073977907
- Cited by
- 128
- References
- 48
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 5 · 2015: 10 · 2014: 9 · 2013: 12 · 2012: 10
- FWCI
- 2.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AI-40488, AI-44072)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
- Health Sciences › Medicine › Infectious Diseases › Infectious Diseases and Tuberculosis
- Keywords
- Mycobacterium tuberculosis, virulence factors, macrophage infection, intracellular bacterial growth, necrosis, apoptosis, TNF-α, bone marrow-derived macrophages, clinical isolates, DNA fragmentation, host defense
- MeSH terms
- Animals, Bone Marrow Cells, Cell Survival, Cells, Cultured, Female, Humans, Macrophages, Mycobacterium tuberculosis, Necrosis, Tuberculosis, Mice, DNA Fragmentation
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