Host factors subverted by Mycobacterium tuberculosis: Potential targets for host directed therapy

Abstract

Introduction

Despite new approaches in the diagnosis and treatment of tuberculosis (TB), it continues to be a major health burden. Several immunotherapies that potentiate the immune response have come up as adjuncts to drug therapies against drug resistant TB strains; however, there needs to be an urgent appraisal of host specific drug targets for improving their clinical management and to curtail disease progression. Presently, various host directed therapies (HDTs) exist (repurposed drugs, nutraceuticals, monoclonal antibodies and immunomodulatory agents), but these mostly address molecules that combat disease progression.

Areas covered

The current review discusses major Mycobacterium tuberculosis (M. tuberculosis) survival paradigms inside the host and presents a plethora of host targets subverted by M. tuberculosis which can be further explored for future HDTs. The host factors unique to M. tuberculosis infection (in humans) have also been identified through an in-silico interaction mapping.

Expert opinion

HDTs could become the next-generation adjunct therapies in order to counter antimicrobial resistance and virulence, as well as to reduce the duration of existing TB treatments. However, current scientific efforts are largely directed toward combatants rather than host molecules co-opted by M. tuberculosis for its survival. This might drive the immune system to a hyper-inflammatory condition; therefore, we emphasize that host factors subverted by M. tuberculosis, and their subsequent neutralization, must be considered for development of better HDTs.

Keywords:

• Host directed therapy (HDT)
• host epigenetic machinery
• host-pathogen interaction
• host transcription factors (TFs)
• tuberculosis (TB)

Acknowledgements

We thank IMTECH, a constituent laboratory of the CSIR, for facilities and financial support. We express our regret for not citing the work of many colleagues due to space constraints.

Declaration of Interest

The authors declare that they have no conflict of interest.

Additional information

Funding

This work was supported by Department of Biotechnology, Ministry of Science and Technology, National Bioscience Award project (GAP-0162) to PG.