Role of alanine racemase mutations in Mycobacterium tuberculosis D-cycloserine resistance

Yoshio Nakatani, Helen K Opel-Reading, Matthias Merker, Diana Machado, Sönke Andres, S Siva Kumar, Danesh Moradigaravand, Francesc Coll, João Perdigão, Isabel Portugal, Thomas Schön, Dina Nair, K R Uma Devi, Thomas A Kohl, Patrick Beckert, Taane G Clark, Gugu Maphalala, Derrick Khumalo, Roland Diel, Kadri KlaosHtin Lin Aung, Gregory M Cook, Julian Parkhill, Sharon J Peacock, Soumya Swaminathan, Miguel Viveiros, Stefan Niemann, Kurt L Krause, Claudio U Köser

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Abstract

A screening of more than 1,500 drug-resistant strains of Mycobacterium tuberculosis revealed evolutionary patterns characteristic of positive selection for three alanine racemase (Alr) mutations. We investigated these mutations using molecular modeling, in vitro MIC testing, as well as direct measurements of enzymatic activity, which demonstrated that these mutations likely confer resistance to d-cycloserine

Original languageEnglish
JournalAntimicrobial Agents and Chemotherapy
Volume61
Issue number12
Early online date2 Oct 2017
DOIs
Publication statusPublished - Dec 2017

Keywords

  • Alanine racemase
  • Cycloserine
  • Mycobacterium tuberculosis complex Mycobacterium bovis Bovine tuberculosis Real-time PCR

UN Sustainable Development Goals (SDGs)

  • SDG 3 - Good Health and Well-Being

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