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

• Author(s): 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
• Date: 2017
• Persistent ID: http://hdl.handle.net/10362/32683
• Origin: Repositório Institucional da UNL
• Subject(s): 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
• Document Type: Journal article
• Language: English
• Contributor(s): Instituto de Higiene e Medicina Tropical (IHMT); Global Health and Tropical Medicine (GHTM); TB, HIV and opportunistic diseases and pathogens (THOP); RUN

Description

Copyright © 2017 Nakatani et al.

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