Orn-mediated c-di-GMP regulates the CRISPR-Cas system to confer stress response in Mycobacterium tuberculosis - PubMed
3 days ago
- #stress response
- #Mycobacterium tuberculosis
- #CRISPR-Cas
- Mycobacterium tuberculosis (Mtb) has a type III-A CRISPR-Cas system with anti-plasmid immune activity.
- The CRISPR-Cas system in Mtb is transcriptionally dependent and primarily counters exogenous nucleic acids via the Csm6 protein, not the Cas10 HD domain.
- The system helps mitigate oxidative stress and antibiotic treatment, mainly through the Cas10 HD domain.
- Oligoribonuclease (Orn) was identified as a regulator of the Mtb CRISPR-Cas system; its deletion increases c-di-GMP levels.
- Biotin-labeled c-di-GMP pull-down identified Rv3058 as a transcriptional regulator; its knockdown boosts cas6 promoter activity.
- c-di-GMP directly modulates Rv3058's transcriptional repressor function, enhancing stress defense via DNA repair, cell envelope maintenance, and iron homeostasis regulation.
- Orn-mediated c-di-GMP regulation of the CRISPR-Cas system aids Mtb's oxidative and antibiotic stress responses.