Related Experiment Video

Updated: Mar 11, 2026

Establishment of a High-throughput Setup for Screening Small Molecules That Modulate c-di-GMP Signaling in Pseudomonas aeruginosa
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Establishment of a High-throughput Setup for Screening Small Molecules That Modulate c-di-GMP Signaling in Pseudomonas aeruginosa

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Orn-mediated c-di-GMP regulates the CRISPR-Cas system to confer stress response in Mycobacterium tuberculosis

Wenjing Yu1,2, Lisha Yuan1, Wei Zhou1

  • 1State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.

Nucleic Acids Research
|March 10, 2026
PubMed

Insights

The Mycobacterium tuberculosis CRISPR-Cas system helps bacteria survive oxidative and antibiotic stress. This defense is regulated by oligoribonuclease (Orn) and cyclic di-GMP (c-di-GMP), activating protective pathways.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • Mycobacterium tuberculosis (Mtb) has a type III-A CRISPR-Cas system with known anti-plasmid activity.
  • The full functional repertoire of the Mtb CRISPR-Cas system, particularly its role beyond plasmid defense, requires further investigation.

Purpose of the Study:

  • To elucidate the in vivo functions of the Mtb CRISPR-Cas system.
  • To identify regulatory mechanisms controlling the Mtb CRISPR-Cas system's activity.

Main Methods:

  • Investigated CRISPR-Cas system activity in Mtb under various stress conditions.
  • Utilized transposon sequencing (Tn-seq) to identify genetic regulators.
  • Performed pull-down assays to identify protein interactions and characterized transcriptional regulation.

Main Results:

  • The Mtb CRISPR-Cas system is transcriptionally regulated and primarily functions via Csm6 against exogenous nucleic acids.
  • The Cas10 HD domain is crucial for mitigating oxidative and antibiotic stress.
  • Oligoribonuclease (Orn) regulates the CRISPR-Cas system by modulating cyclic di-GMP (c-di-GMP) levels, which in turn affects the transcriptional repressor Rv3058.
  • This pathway activates stress defense mechanisms including DNA repair and iron homeostasis.

Conclusions:

  • The Mtb CRISPR-Cas system plays a significant role in stress adaptation beyond plasmid immunity.
  • Orn-mediated c-di-GMP signaling is a key regulatory mechanism controlling the CRISPR-Cas system's contribution to Mtb's survival under stress.

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