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Role of Alanine Racemase Mutations in Mycobacterium tuberculosis D-Cycloserine Resistance
University of Otago, New Zealand; University of Auckland, New Zealand; University of Otago, New Zealand.
University of Otago, New Zealand.
Research Centre Borstel, Germany; German Centre Infect Research, Germany.
University of Nova Lisboa, Portugal.
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2017 (English)In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 61, no 12, article id e01575-17Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
AMER SOC MICROBIOLOGY , 2017. Vol. 61, no 12, article id e01575-17
Keyword [en]
Mycobacterium tuberculosis; cycloserine; alanine racemase
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:liu:diva-143722DOI: 10.1128/AAC.01575-17ISI: 000416578900061PubMedID: 28971867OAI: oai:DiVA.org:liu-143722DiVA, id: diva2:1166744
Note

Funding Agencies|University of Otago; Health Research Council; Maurice Wilkins Centre; European Union [FP7-278864-2]; German Center for Infection Research (DZIF); Fundacao para a Ciencia e a Tecnologia, Portugal [UID/Multi/04413/2013, SFRH/BPD/100688/2014, SFRH/BPD/95406/2013]; Wellcome Trust [201344/Z/16/Z]; Medical Research Council UK [MR/K000551/1, MR/M01360X/1, MR/N010469/1]; Indian Council of Medical Research, New Delhi; L2 Diagnostics LLC, New Haven; Pacific Biosciences, Inc.; Illumina, Inc.; European Society of Mycobacteriology; Hain Lifescience; UK Department of Health [HICF-T5-342, WT098600]; Wellcome Trust

Available from: 2017-12-15 Created: 2017-12-15 Last updated: 2018-01-26

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