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

*Corresponding author for this work
12 Citations (Scopus)


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
Article numbere01575
JournalAntimicrobial Agents and Chemotherapy
Issue number12
Publication statusPublished - 12.2017

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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