Pyrazinamide—Old TB Drug Finds New Target

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Science  16 Sep 2011:
Vol. 333, Issue 6049, pp. 1583-1584
DOI: 10.1126/science.1212450

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More than 60 years after the discovery of pyrazinamide (PZA), a drug that is a mainstay of combination therapy for tuberculosis (TB), researchers have finally uncovered a mechanism of action that is convincing and novel. On page 1630 of this issue, Shi et al. (1) show that PZA inhibits trans-translation, a key cellular process for managing damaged proteins and “rescuing” nonfunctioning ribosomes, in Mycobacterium tuberculosis. The finding identifies a potentially promising target for new drugs.