Role of Alanine Racemase Mutations in Mycobacterium tuberculosis d-Cycloserine Resistance.
Yoshio NakataniHelen K Opel-ReadingMatthias MerkerDiana MachadoSönke AndresS Siva KumarDanesh MoradigaravandFrancesc CollJoão PerdigãoIsabel PortugalThomas SchönDina NairK R Uma DeviThomas A KohlPatrick BeckertTaane Gregory ClarkGugu MaphalalaDerrick KhumaloRoland DielKadri KlaosHtin Lin AungGregory M CookJulian ParkhillSharon J PeacockSoumya SwaminathanMiguel ViveirosStefan NiemannKurt L KrauseClaudio Umberto KöserPublished in: Antimicrobial agents and chemotherapy (2017)
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.