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Ancient and recent differences in the intrinsic susceptibility of Mycobacterium...

Bateson, Anna; Canseco, Julio Ortiz; McHugh, Timothy D.; Witney, Adam A.; Feuerriegel, Silke; Merker, Matthias; Kohl, Thomas A.; Utpatel, Christian

Objectives: To develop a robust phenotypic antimicrobial susceptibility testing (AST) method with a correctly set breakpoint for pretomanid (Pa), the most recently approved anti-tuberculosis drug. Methods: The Becton Dickinson Mycobacterial Growth Indicator Tube™ (MGIT) system was used at six laboratories to determine the MICs of a phylogenetically diverse collection of 356 Mycobacterium tuberculosis complex (M...


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

Nakatani, Yoshio; Opel-Reading, Helen K; Merker, Matthias; Machado, Diana; Andres, Sönke; Kumar, S Siva; Moradigaravand, Danesh; Coll, Francesc

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 con...


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