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Role of Alanine Racemase Mutations in Mycobacterium tuberculosis d-Cycloserine Resistance.

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.

SUBMITTER: Nakatani Y

PROVIDER: S-EPMC5700341 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Role of Alanine Racemase Mutations in Mycobacterium tuberculosis d-Cycloserine Resistance.

Nakatani Yoshio Y Opel-Reading Helen K HK Merker Matthias M Machado Diana D Andres Sönke S Kumar S Siva SS Moradigaravand Danesh D Coll Francesc F Perdigão João J Portugal Isabel I Schön Thomas T Nair Dina D Devi K R Uma KRU Kohl Thomas A TA Beckert Patrick P Clark Taane G TG Maphalala Gugu G Khumalo Derrick D Diel Roland R Klaos Kadri K Aung Htin Lin HL Cook Gregory M GM Parkhill Julian J Peacock Sharon J SJ Swaminathan Soumya S Viveiros Miguel M Niemann Stefan S Krause Kurt L KL Köser Claudio U CU

Antimicrobial agents and chemotherapy 20171122 12

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. ...[more]

PMID: 28971867

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Structure of the d-Cycloserine-Resistant Variant D322N of Alanine Racemase from Mycobacterium tuberculosis.

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Overexpression of the D-alanine racemase gene confers resistance to D-cycloserine in Mycobacterium smegmatis.

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Correction to Reinterpreting the Mechanism of Inhibition of Mycobacterium tuberculosis d-Alanine:d-Alanine Ligase by d-Cycloserine.

Project description: Not available

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Ethambutol resistance in Mycobacterium tuberculosis: critical role of embB mutations.

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