Transcription attenuation amplifies collateral vulnerabilities in rifampicin-resistant Mycobacterium tuberculosis - PubMed
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- #tuberculosis
- #antibiotic resistance
- #CRISPRi
- Rifampicin resistance in Mycobacterium tuberculosis often involves RNA polymerase mutations like βS450L, which cause antibiotic resistance and physiological changes.
- CRISPRi functional genomics identified specific vulnerabilities in βS450L mutants, including impaired thiamine and branched-chain amino acid (BCAA) biosynthesis pathways.
- Transcription attenuation in βS450L mutants reduces their ability to upregulate ilvB1 expression, leading to collateral vulnerabilities.
- The study highlights distinct physiological impacts of rifampicin resistance and suggests potential targeted interventions for drug-resistant strains.