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

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Detalhes bibliográficos
Resumo: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
Autores principais:Nakatani, Yoshio
Outros Autores:Opel-Reading, Helen K; Merker, Matthias; Machado, Diana; Andres, Sönke; Kumar, S Siva; Moradigaravand, Danesh; Coll, Francesc; Perdigão, João; Portugal, Isabel; Schön, Thomas; Nair, Dina; Devi, K R Uma; Kohl, Thomas A; Beckert, Patrick; Clark, Taane G; Maphalala, Gugu; Khumalo, Derrick; Diel, Roland; Klaos, Kadri; Aung, Htin Lin; Cook, Gregory M; Parkhill, Julian; Peacock, Sharon J; Swaminathan, Soumya; Viveiros, Miguel; Niemann, Stefan; Krause, Kurt L; Köser, Claudio U
Assunto:Alanine racemase Cycloserine Mycobacterium tuberculosis complex Mycobacterium bovis Bovine tuberculosis Real-time PCR Biochemistry, Genetics and Molecular Biology (miscellaneous) Infectious Diseases SDG 3 - Good Health and Well-being
Ano:2017
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade Nova de Lisboa
Idioma:inglês
Origem:Repositório Institucional da UNL
Descrição
Resumo: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