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Year : 2008  |  Volume : 26  |  Issue : 4  |  Page : 342-348

Progression of chronic pulmonary tuberculosis in mice intravenously infected with ethambutol resistant Mycobacterium tuberculosis

1 Department of Internal Medicine/Infectious Diseases, UT Southwestern Medical Center at Dallas, Texas-75390, USA
2 Indian Council of Medical Research, New Delhi, India
3 Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
4 Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
5 Department of Environmental Science, Babasaheb Bhimrao Ambedkar University, Lucknow, India

Correspondence Address:
A Ayyagari
Indian Council of Medical Research, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0255-0857.42124

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Purpose: Ethambutol (EMB) is an important first line drug, however little information on its molecular mechanism of resistance and pathogenicity of resistant isolates is available. Present work was designed to study virulence of the EMB resistant M. tuberculosis strains and the host responses in-vivo on infection of EMB resistant M. tuberculosis using Balb/c mouse model of infection. Methods: Three groups of Balb/c mice (female, age 4-6 wk; 21 mice in each group) were infected intravenously with 106 CFU of M. tuberculosis H37Rv and two EMB resistant clinical isolates. Age and sex matched control animals were mock inoculated with Middlebrook 7H9 broth alone. At 10, 20, 30, 40, 50, 60, and 70 days post-infection three animals from each group were sacrificed by cervical dislocation and lung tissue was collected for further analysis. Results: Infection with EMB resistant M. tuberculosis led to progressive and chronic disease with significantly high bacillary load (p=0.02). Massive infiltration and exacerbated lung pathology with increased expression of IFN-γ and TNF-α was observed in lungs of mice infected with EMB resistant strains. The present study suggests that infection with EMB resistant M. tuberculosis leads to chronic infection with subsequent loss of lung function, bacterial persistence with elevated expression of TNF-α resulting in increased lung pathology. Conclusion: These findings highlight that EMB resistant M. tuberculosis regulates host immune response differentially and its pathogenicity is different from drug sensitive strains of M. tuberculosis.


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2004 - Indian Journal of Medical Microbiology
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