Research ArticleTuberculosis

Targeting protein biotinylation enhances tuberculosis chemotherapy

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Science Translational Medicine  25 Apr 2018:
Vol. 10, Issue 438, eaal1803
DOI: 10.1126/scitranslmed.aal1803

A new drug target for combatting TB

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB). The paucity of validated drug targets limits efforts to develop new drugs to combat TB. New work by Tiwari et al. establishes bacterial biotin protein ligase (BPL), the enzyme Mtb requires to covalently attach the essential vitamin biotin to biotin-dependent enzymes, as an alternative frontline target in the development of drugs against TB. These investigators demonstrated that inactivation of BPL killed Mtb in vitro and eradicated this pathogen from infected mice. Inhibition of protein biotinylation increased the potency of the frontline TB drug rifampicin both in vitro and during infection of mice.

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