Key Findings

The study identifies two distinct mechanisms of pyrazinamide resistance: (1) missense mutations in the aspartate decarboxylase panD, which prevent pyrazinoic acid (POA)-mediated coenzyme A (CoA) depletion, and (2) loss-of-function mutations in the polyketide synthases mas and ppsA-E, which affect the synthesis of the virulence factor phthiocerol dimycocerosate (PDIM).