Role of Alanine Racemase Mutations in Mycobacterium tuberculosis D-Cycloserine Resistance

Yoshio Nakatani; Helen K. Opel-Reading; Matthias Merker; Diana Machado; Sonke Andres; S. Siva Kumar; Danesh Moradigaravand; Francesc Coll; Joao Perdigao; Isabel Portugal; Thomas Schon; Dina Nair; K. R. Uma Devi; Thomas A. Kohl; Patrick Beckert; Taane G. Clark; Gugu Maphalala; Derrick Khumalo; Roland Diel; Kadri Klaos; Htin Lin Aung; Gregory M. Cook; Julian Parkhill; Sharon J. Peacock; Soumya Swaminathan; Miguel Viveiros; Stefan Niemann; Kurt L. Krause; Claudio U. Koser

doi:10.1128/AAC.01575-17

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Role of Alanine Racemase Mutations in Mycobacterium tuberculosis D-Cycloserine Resistance

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Role of Alanine Racemase Mutations in Mycobacterium tuberculosis D-Cycloserine Resistance

Yoshio Nakatani, Helen K. Opel-Reading, Matthias Merker, Diana Machado, Sonke Andres, S. Siva Kumar, Danesh Moradigaravand, Francesc Coll, Joao Perdigao, Isabel Portugal, …

Antimicrobial agents and chemotherapy, Vol.61(12), 01575

01/12/2017

DOI: https://doi.org/10.1128/AAC.01575-17

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https://hdl.handle.net/10523/26665

Abstract

Life Sciences & Biomedicine

Microbiology

Pharmacology & Pharmacy

Science & Technology

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.

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Record Identifier: 9926515360601891
Title: Role of Alanine Racemase Mutations in Mycobacterium tuberculosis D-Cycloserine Resistance
Creators: Yoshio Nakatani
Helen K. Opel-Reading
Matthias Merker
Diana Machado
Sonke Andres
S. Siva Kumar
Danesh Moradigaravand
Francesc Coll
Joao Perdigao
Isabel Portugal
Thomas Schon
Dina Nair
K. R. Uma Devi
Thomas A. Kohl
Patrick Beckert
Taane G. Clark
Gugu Maphalala
Derrick Khumalo
Roland Diel
Kadri Klaos
Htin Lin Aung
Gregory M. Cook
Julian Parkhill
Sharon J. Peacock
Soumya Swaminathan
Miguel Viveiros
Stefan Niemann
Kurt L. Krause
Claudio U. Koser
Publication Details: Antimicrobial agents and chemotherapy, Vol.61(12), 01575
Academic Unit: Biochemistry; Microbiology and Immunology
Publisher: Amer Soc Microbiology
Grant note: Wellcome Trust European Society of Mycobacteriology Hain Lifescience MR/M01360X/1; MR/N010469/1 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Maurice Wilkins Centre MR/K000551/1; MR/N010469/1; MR/M01360X/1 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Health Research Council; Health Research Council of New Zealand UID/Multi/04413/2013; SFRH/BPD/100688/2014; SFRH/BPD/95406/2013 / Fundacao para a Ciencia e a Tecnologia, Portugal; Fundacao para a Ciencia e a Tecnologia (FCT) MR/K000551/1; MR/M01360X/1; MR/N010469/1 / Medical Research Council UK; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Illumina, Inc. University of Otago Indian Council of Medical Research, New Delhi; Indian Council of Medical Research (ICMR) L2 Diagnostics LLC, New Haven FP7-278864-2 / European Union; European Union (EU) German Center for Infection Research (DZIF) 201344/Z/16/Z / Wellcome Trust HICF-T5-342; WT098600 / UK Department of Health; National Institutes of Health Research (NIHR) Pacific Biosciences, Inc.
Date published ; e-published: 01/12/2017
Language: English
Resource Type ; Subtype: Journal article