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

Yoshio Nakatani; Helen K. Opel-Reading; Matthias Merker; Diana Machado; Sönke Andres; S. Siva Kumar; Danesh Moradigaravand; Francesc Coll; João Perdigão; Isabel Portugal; Thomas Schön; 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. Köser

doi:10.1128/AAC.01575-17

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

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

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

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.

Original language	English (US)
Journal	Antimicrobial Agents and Chemotherapy
Volume	61
Issue number	12
DOIs	https://doi.org/10.1128/AAC.01575-17
State	Published - Dec 1 2017
Externally published	Yes

ASJC Scopus subject areas

Infectious Diseases
Pharmacology
Pharmacology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1128/AAC.01575-17

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Nakatani, Y., Opel-Reading, H. K., Merker, M., Machado, D., Andres, S., Kumar, S. S., Moradigaravand, D., Coll, F., Perdigão, J., Portugal, I., Schön, T., Nair, D., Devi, K. R. U., Kohl, T. A., Beckert, P., Clark, T. G., Maphalala, G., Khumalo, D., Diel, R., ... Köser, C. U. (2017). Role of alanine racemase mutations in Mycobacterium tuberculosis D-cycloserine resistance. Antimicrobial Agents and Chemotherapy, 61(12). https://doi.org/10.1128/AAC.01575-17

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title = "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.",

author = "Yoshio Nakatani and Opel-Reading, {Helen K.} and Matthias Merker and Diana Machado and S{\"o}nke Andres and Kumar, {S. Siva} and Danesh Moradigaravand and Francesc Coll and Jo{\~a}o Perdig{\~a}o and Isabel Portugal and Thomas Sch{\"o}n and Dina Nair and Devi, {K. R.Uma} and Kohl, {Thomas A.} and Patrick Beckert and Clark, {Taane G.} and Gugu Maphalala and Derrick Khumalo and Roland Diel and Kadri Klaos and Aung, {Htin Lin} and Cook, {Gregory M.} and Julian Parkhill and Peacock, {Sharon J.} and Soumya Swaminathan and Miguel Viveiros and Stefan Niemann and Krause, {Kurt L.} and K{\"o}ser, {Claudio U.}",

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Nakatani, Y, Opel-Reading, HK, Merker, M, Machado, D, Andres, S, Kumar, SS, Moradigaravand, D, Coll, F, Perdigão, J, Portugal, I, Schön, T, Nair, D, Devi, KRU, Kohl, TA, Beckert, P, Clark, TG, Maphalala, G, Khumalo, D, Diel, R, Klaos, K, Aung, HL, Cook, GM, Parkhill, J, Peacock, SJ, Swaminathan, S, Viveiros, M, Niemann, S, Krause, KL & Köser, CU 2017, 'Role of alanine racemase mutations in Mycobacterium tuberculosis D-cycloserine resistance', Antimicrobial Agents and Chemotherapy, vol. 61, no. 12. https://doi.org/10.1128/AAC.01575-17

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T1 - Role of alanine racemase mutations in Mycobacterium tuberculosis D-cycloserine resistance

AU - Nakatani, Yoshio

AU - Opel-Reading, Helen K.

AU - Merker, Matthias

AU - Machado, Diana

AU - Andres, Sönke

AU - Kumar, S. Siva

AU - Moradigaravand, Danesh

AU - Coll, Francesc

AU - Perdigão, João

AU - Portugal, Isabel

AU - Schön, Thomas

AU - Nair, Dina

AU - Devi, K. R.Uma

AU - Kohl, Thomas A.

AU - Beckert, Patrick

AU - Clark, Taane G.

AU - Maphalala, Gugu

AU - Khumalo, Derrick

AU - Diel, Roland

AU - Klaos, Kadri

AU - Aung, Htin Lin

AU - Cook, Gregory M.

AU - Parkhill, Julian

AU - Peacock, Sharon J.

AU - Swaminathan, Soumya

AU - Viveiros, Miguel

AU - Niemann, Stefan

AU - Krause, Kurt L.

AU - Köser, Claudio U.

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PY - 2017/12/1

Y1 - 2017/12/1

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AB - 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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ER -

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

Abstract

ASJC Scopus subject areas

UN SDGs

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