Genome scale CRISPRi reveals both shared and strain-specific vulnerabilities in genetically diverse drug-resistant strains of Mycobacterium tuberculosis - PubMed
4 hours ago
- #tuberculosis
- #drug resistance
- #CRISPRi
- Genome-scale CRISPRi identified shared and strain-specific vulnerabilities in drug-resistant Mycobacterium tuberculosis.
- Drug-resistant strains were more sensitive to tRNA synthetase knockdowns, suggesting them as high-value drug targets.
- Rifampicin-resistant mutant RpoB(S450L) showed increased vulnerability to sulphur metabolism dysregulation, linked to transcriptional changes.
- Clinical isolates evolved mutations in sulphur metabolism genes to mitigate fitness costs from drug resistance collateral effects.
- Functional genomics is powerful for pinpointing vulnerable drug targets across diverse drug-resistant strains.