Expression of Bcl-2 family
protein,
Bfl-1/A1 has been found to differ considerably amongst macrophages infected with virulent Mycobacterium tuberculosis H37Rv or with avirulent M.
tuberculosis H37Ra. Present work was undertaken to deduce the significance of differential expression of
Bfl-1/A1 in the outcome of mycobacterial
infection. We have studied the role of
Bfl-1/A1 particularly in autophagy formation in tubercle bacilli infected cells since autophagy has been recognized as a component of innate immunity against pathogenic mycobacteria. First, we have confirmed that upon
infection virulent strain H37Rv retain
Bfl-1/A1 for longer period and impose autophagosome maturation block within infected cells as evident from confocal microscopy. Moreover, down regulation of
Bfl-1/A1 by
siRNA induced autophagy formation and reduced bacterial growth. Furthermore, even the avirulent strain H37Ra resist autophagosome maturation and survive if the cellular level of Bfl-1 is maintained in THP-1 cells by stable transfection (
Bfl-1 overexpressing cells). No noteworthy difference in mTOR expression was observed between normal THP-1 and Bfl-1 overexpressing THP-1 cells infected with either strain of mycobacteria. Interestingly, we found that not only mTOR but also
Bfl-1/A1 is involved in
rapamycin induced autophagy in mycobacteria infected macrophages. We have found that Bfl-1 physically interacts with
Beclin 1 in Bfl-1 overexpressing THP-1 as well as in H37Rv infected THP-1 cells as they co-precipitated. Taken together, our results clearly demonstrated that
Bfl-1/A1 negatively regulates autophagy and expression of
Bfl-1/A1 in H37Rv infected macrophages provides the bacteria a survival strategy to overcome host defense.