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

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 measur...

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Autores principales: Nakatani, Yoshio, 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2017
Materias:
Mechanisms of Resistance
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700341/
https://www.ncbi.nlm.nih.gov/pubmed/28971867
http://dx.doi.org/10.1128/AAC.01575-17
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author Nakatani, Yoshio
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.
author_facet Nakatani, Yoshio
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.
author_sort Nakatani, Yoshio
collection PubMed
description 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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spelling pubmed-57003412017-12-01 Role of Alanine Racemase Mutations in Mycobacterium tuberculosis d-Cycloserine Resistance Nakatani, Yoshio 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. Antimicrob Agents Chemother Mechanisms of Resistance 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. American Society for Microbiology 2017-11-22 /pmc/articles/PMC5700341/ /pubmed/28971867 http://dx.doi.org/10.1128/AAC.01575-17 Text en Copyright © 2017 Nakatani et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Mechanisms of Resistance
Nakatani, Yoshio
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.
Role of Alanine Racemase Mutations in Mycobacterium tuberculosis d-Cycloserine Resistance
title Role of Alanine Racemase Mutations in Mycobacterium tuberculosis d-Cycloserine Resistance
title_full Role of Alanine Racemase Mutations in Mycobacterium tuberculosis d-Cycloserine Resistance
title_fullStr Role of Alanine Racemase Mutations in Mycobacterium tuberculosis d-Cycloserine Resistance
title_full_unstemmed Role of Alanine Racemase Mutations in Mycobacterium tuberculosis d-Cycloserine Resistance
title_short Role of Alanine Racemase Mutations in Mycobacterium tuberculosis d-Cycloserine Resistance
title_sort role of alanine racemase mutations in mycobacterium tuberculosis d-cycloserine resistance
topic Mechanisms of Resistance
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700341/
https://www.ncbi.nlm.nih.gov/pubmed/28971867
http://dx.doi.org/10.1128/AAC.01575-17
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