Nucleoid-associated protein HU constrains transcription elongation to influence cellular functions, virulence, and drug tolerance in Mycobacterium tuberculosis - PubMed
5 hours ago
- #antibiotic tolerance
- #Mycobacterium tuberculosis
- #transcription regulation
- Nucleoid-associated protein HU (MtHU) is essential for Mycobacterium tuberculosis (Mtb) and plays a key role in organizing chromosome architecture and regulating gene expression.
- Conditional depletion of MtHU leads to transcriptional deregulation of over 800 genes involved in various cellular processes, highlighting its dominant role in gene control.
- ChIP-seq analysis shows widespread MtHU binding across the genome, including intergenic regions and within gene bodies, which hampers RNA polymerase elongation during transcription.
- MtHU depletion results in gene upregulation, indicating its predominant negative regulatory role in transcription.
- Limiting MtHU during Mtb infection reduces intracellular survival and antibiotic tolerance, linking its regulatory function to host-pathogen dynamics and drug resistance.
- The study expands the functional landscape of MtHU, revealing its roles in transcriptional control, immune modulation, and antibiotic tolerance, offering potential for new treatment strategies.