Journal
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY
Volume 10, Issue 9, Pages 971-981Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1586/ERI.12.87
Keywords
antifolates; ethionamide; mycobacterium; potentiation; targeting resistance; tuberculosis
Funding
- US NIH [R01AI087903]
- STERIS Infectious Diseases Research Support Grant
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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.
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