Role of alanine racemase mutations in Mycobacterium tuberculosis D-cycloserine resistance
- Autores: Andres S, Aung HL, Beckert P, Clark TG, Coll F, Cook GM, Devi KRU, Diel R, Khumalo D, Klaos K, Kohl TA, Köser CU, Krause KL, Kumar SS, Machado D, Maphalala G, Merker M, Moradigaravand D, Nair D, Nakatani Y, Niemann S, Opel-Reading HK, Parkhill J, Peacock SJ, Perdigão J, Portugal I, Schön T, Swaminathan S, Viveiros M
- Ano de Publicação: 2017
- Journal: Antimicrobial Agents and Chemotherapy
- Link: https://www.ncbi.nlm.nih.gov/pubmed/28971867
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.