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Ethambutol is one of the backbone agents for the management of Mycobacterium tuberculosis (Mtb) infections and of other pathogenic mycobacterial species. Its antimicrobial effect is known to be related to interaction with three membrane-embedded arabinosyltransferases — EmbA, EmbB, and EmbC — involved in the synthesis of the mycobacterial cell wall. However, its exact mechanism of action has been unclear. Investigators have now used x-ray crystallographic techniques to define the structural basis of ethambutol's inhibitory activity.
The investigators purified EmbA, EmbB, and EmbC from both Mtb and Mycobacterium smegmatis and showed that these arabinosyltransferases were biologically active in cell-free assays. The investigators used single c…