Strategies for potentiation of ethionamide and folate antagonists against Mycobacterium tuberculosis

Abstract

Antifolates inhibit de novo folate biosynthesis, whereas ethionamide targets the mycolate synthetic pathway in Mycobacterium tuberculosis. These antibiotics are effective against M. tuberculosis but their use has been hampered by concerns over toxicity and low therapeutic indexes. With the increasing spread of drug-resistant forms, interest in using old drugs for tuberculosis treatment has been renewed. Specific inhibitors targeting resistance mechanisms could sensitize M. tuberculosis to these available, clinically approved drugs. This review discusses recently developed strategies to boost the antituberculous activity of ethionamide and antifolates. These approaches might help broaden the currently limited chemotherapeutic options of not only drug-resistant but also drug-susceptible tuberculosis, which still remains one of the most common infectious diseases in the developing world.

Keywords::

• antifolates
• ethionamide
• mycobacterium
• potentiation
• targeting resistance
• tuberculosis

Acknowledgements

The authors thank Kien Nguyen and Henry Boom for critical reading and comments on the manuscript.

Financial & competing interests disclosure

Work in the Nguyen laboratory is supported by the US NIH (R01AI087903) and a STERIS Infectious Diseases Research Support Grant. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.