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 ({Delta}438A) in RpsA associated with PZA resistance, but its role in PZA resistance is controversial. Here, we introduced RpsA mutation {Delta}438A or D123A into M. tuberculosis chromosome and demonstrated that the introduced RspA mutations are indeed responsible for PZA resistance.