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

A screening of more than 1,500 drug-resistant strains of revealed evolutionary patterns characteristic of positive selection for three alanine racemase (Alr) mutations. We investigated these mutations using molecular modeling, MIC testing, as well as direct measurements of enzymatic activity, which...

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Veröffentlicht in:	Antimicrobial agents and chemotherapy 2017-12, Vol.61 (12)
Hauptverfasser:	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
Format:	Artikel
Sprache:	eng
Schlagworte:	Alanine Racemase - genetics Alanine Racemase - metabolism Antibiotics, Antitubercular - pharmacology Bacterial Proteins - genetics Bacterial Proteins - metabolism Cycloserine - pharmacology Drug Resistance, Bacterial - genetics Evolution, Molecular Gene Expression Mechanisms of Resistance Microbial Sensitivity Tests Mutation Mycobacterium tuberculosis - classification Mycobacterium tuberculosis - drug effects Mycobacterium tuberculosis - enzymology Mycobacterium tuberculosis - genetics Phylogeny Selection, Genetic
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Beschreibung
Zusammenfassung:	A screening of more than 1,500 drug-resistant strains of revealed evolutionary patterns characteristic of positive selection for three alanine racemase (Alr) mutations. We investigated these mutations using molecular modeling, MIC testing, as well as direct measurements of enzymatic activity, which demonstrated that these mutations likely confer resistance to d-cycloserine.
ISSN:	0066-4804 1098-6596 1098-6596
DOI:	10.1128/AAC.01575-17