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Advancing host-directed Methods: We have used novel AKT inhibitor against MTB infected
macrophage and tested its survivability and its molecular mechanism
of killing inside macrophage.
therapy for tuberculosis/MDR- Result: In the present work mouse peritoneal macrophages infected

TB: Development of novel AKT with pathogenic strain of M.tb (H37Rv) exhibited increased
phosphorylation of AKT. Interestingly, suppression of AKT
activity by a novel small molecule inhibitor during mycobacterial
inhibitors as an adjunctive infection promoted phagolysosome fusion, apoptosis and autophagy,
altogether contributing towards reduction in bacterial count in vitro.
treatment for tuberculosis At the molecular level, we noticed that, small molecule inhibitor
to AKT treatment deciphered the requirement of phosphorylation
of AS160, Bad and mTOR by phosphorylated AKT in infected
Nikhila Meda1, Dharmarajan Sriram1 macrophages. Additionally, inhibition of phosphorylated AKT
Department of Pharmacy, Birla Institute of Technology & Science-Pilani,
1 hampered nuclear translocation of NF-kB resulting in decreased
Hyderabad Campus, Hyderabad-500078, India. cytokine expression.

Aim and Objective: Previous studies reported the implications of
host-immune cell signalling pathways contributing towards survival
of mycobacteria. Among the few, abrogation of PI3K-AKT-mTOR
pathway has been shown to impact bacterial viability in macrophages.
However, the intricate molecular mechanisms associated with such
outcome at the juncture of host-pathogen interaction remain elusive.
Conclusion: Taken together, our inhibitor can be utilized as an
adjunctive therapy, as it shows high efficacy in decreasing bacterial
count in combination with standard drugs to TB and also prevent
the development of antibiotic resistance as host pathways are being
targeted.
Key words: Host directed therapy, Adjunctive therapy, AKT inhibitors

S70 © 2020 International Journal of Mycobacteriology | Published by Wolters Kluwer - Medknow