Analysis of a novel pncA mutation for susceptibility to Pyrazinamide therapy

Abstract

Pyrazinamide (PZA), which is an analogue of nicotinamide, is an important first-line drug used in the short-course treatment of tuberculosis. PZA is a prodrug devoid of significant antibacterial activity. It is metabolized into its active form, pyrazinoic acid (POA), by the amidase activity of the Mycobacterium tuberculosis nicotinamidase/pyrazinamidase, encoded by the pncA gene. Mutations in pncA that prevent activation of the prodrug represent the major mechanism of PZA resistance in M. tuberculosis [1]. This antibiotic plays a key role in shortening the duration of anti-tuberculous treatment due to its activity against the persisting tubercle bacilli at acidic pH.