Introducing RpsA Point Mutation Δ438A or D123A into the Chromosome of M. tuberculosis Confirms its Role in Causing Resistance to Pyrazinamide

ABSTRACT Pyrazinamide (PZA) is a unique frontiline drug for shortening tuberculosis treatment, but its mechanisms of action are elusive. We previously identified RpsA as a target of PZA and found an alanine deletion at position 438 (Δ438A) in RpsA associated with PZA resistance, but its role in PZA resistance is controversial. Here, we introduced RpsA mutation Δ438A or D123A into M. tuberculosis chromosome and demonstrated that the introduced RspA mutations are indeed responsible for PZA resistance.