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Antimicrob Agents Chemother. 2019 Mar 11. pii: AAC.02681-18. doi: 10.1128/AAC.02681-18. [Epub ahead of print]

Introducing RpsA Point Mutations Δ438A and D123A into the Chromosome of M. tuberculosis Confirms their Role in Causing Resistance to Pyrazinamide.

Author information

1
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
2
Lanzhou Center for Tuberculosis Research and Institute of Pathogenic Biology & Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
3
Unit for Genome Dynamics, Department of Microbiology, Oslo University Hospital, University of Oslo, Norway.
4
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA yzhang@jhsph.edu.

Abstract

Pyrazinamide (PZA) is a unique frontline drug for shortening tuberculosis (TB) treatment, but its mechanisms of action are elusive. We previously found one PZA-resistant strain that harbors an alanine deletion at position 438 (Δ438A) in RpsA, a target of PZA, associated with PZA resistance, but its role in causing PZA resistance has been inconclusive. Here, we introduced the RpsA Δ438A mutation along with the D123A mutation into Mycobacterium tuberculosis chromosome and demonstrated that these RspA mutations are indeed responsible for PZA resistance.

PMID:
30858213
DOI:
10.1128/AAC.02681-18

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