ArticleNature communications2024
Whole genome CRISPRi screening identifies druggable vulnerabilities in an isoniazid resistant strain of Mycobacterium tuberculosis.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Dual inhibition of respiratory complexes inMicrobiology spectrum · 2026Article
- Article
- Genome scale CRISPRi reveals both shared and strain-specific vulnerabilities in genetically diverse drug-resistant strains of Mycobacterium tuberculosis.Nature communications · 2026Article
- Transcription attenuation amplifies collateral vulnerabilities in rifampicin-resistant Mycobacterium tuberculosis.Nature microbiology · 2026Article
- Metabolic perturbation reduces antibiotic tolerance inMicrobiology (Reading, England) · 2026Article
- CRISPR screening redefines therapeutic target identification and drug discovery with precision and scalability.Journal of pharmaceutical analysis · 2026Review
- Advancing Tuberculosis Treatment with Next-Generation Drugs and Smart Delivery Systems.Pharmaceutics · 2026Review
- CRISPR-based genetic tools for the study of host-microbe interactions.Infection and immunity · 2025Review
- Metabolic rewiring of isoniazid sensitivity inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Genetic determinants ofMicrobiology spectrum · 2025Article
- The role of bacterial metabolism in antimicrobial resistance.Nature reviews. Microbiology · 2025Review
- Structure and assembly of the MmpL5/MmpS5 efflux transporter from Mycobacterium tuberculosis.Nature communications · 2025Article
- Verapamil and its metabolite norverapamil inhibit theProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Dietary Fibre Modulates Body Composition, Blood Glucose, Inflammation, Microbiome, and Metabolome in a Murine Model of Periodontitis.Nutrients · 2025Article
- Catalase activity deficiency sensitizes multidrug-resistant Mycobacterium tuberculosis to the ATP synthase inhibitor bedaquiline.Nature communications · 2024Article
- Whole genome CRISPRi screening identifies druggable vulnerabilities in an isoniazid resistant strain of Mycobacterium tuberculosis.Nature communications · 2024Article
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Authors and funding
18 authors.
Funding
Abstract
Drug-resistant strains of Mycobacterium tuberculosis are a major global health problem. Resistance to the front-line antibiotic isoniazid is often associated with mutations in the katG-encoded bifunctional catalase-peroxidase. We hypothesise that perturbed KatG activity would generate collateral vulnerabilities in isoniazid-resistant katG mutants, providing potential pathway targets to combat isoniazid resistance. Whole genome CRISPRi screens, transcriptomics, and metabolomics were used to generate a genome-wide map of cellular vulnerabilities in an isoniazid-resistant katG mutant strain of M. tuberculosis. Here, we show that metabolic and transcriptional remodelling compensates for the loss of KatG but in doing so generates vulnerabilities in respiration, ribosome biogenesis, and nucleotide and amino acid metabolism. Importantly, these vulnerabilities are more sensitive to inhibition in an isoniazid-resistant katG mutant and translated to clinical isolates. This work highlights how changes in the physiology of drug-resistant strains generates druggable vulnerabilities that can be exploited to improve clinical outcomes.
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