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Updated: Apr 24, 2026

System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis
Published on: April 5, 2017
Metabolic perturbation reduces antibiotic tolerance in Mycobacterium tuberculosis
Chen-Yi Cheung1, Imogen Samuels1, Hannah R Klaus1
1Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
None:
Mycobacterium tuberculosis is tolerant to many antibiotics, leading to impaired antibiotic killing. Using CRISPR interference (CRISPRi) transcriptional knockdowns, we generated a panel of metabolically compromised strains to identify tolerance pathways for pursuing in therapeutic development. Disrupting the regulation of intracellular iron storage, amino acid biosynthesis and redox defence mechanisms potentiated the lethality of multiple drugs and translated to infected THP-1 macrophages. This work reinforces the role of metabolism as a major contributor to drug tolerance in M. tuberculosis.
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