Phenotypic drug susceptibility testing shows resistance to pyrazinamide in an M. tuberculosis isolate. Mutations in which gene account for the large majority of pyrazinamide resistance?

• A rpsA, encoding ribosomal protein S1
• B embB, encoding arabinosyltransferase
• C pncA, encoding pyrazinamidase ✓
• D inhA promoter region

Explanation

Pyrazinamide is a prodrug converted to active pyrazinoic acid by the bacterial pyrazinamidase encoded by pncA. Loss-of-function mutations in pncA explain most pyrazinamide resistance worldwide, which is why pncA sequencing is proposed as a molecular marker for PZA resistance. embB mutations confer ethambutol resistance and inhA promoter mutations confer isoniazid resistance. rpsA and panD are rare alternative loci, not the major mechanism.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.