Medknow Publications on behalf of Indian Association of Medical Microbiology
Abstract
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