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TitlePotential role of a CRISPR-Cas-activated toxin-antitoxin system in bacterial immunity.
Journal, issue, pagesNat Commun, Vol. 17, Issue 1, Year 2026
Publish dateJun 26, 2026
AuthorsJiyun Chen / Linglong Huang / Hong Chen / Xueyan Li / Xiaofeng Lin / Chenmin Guo / Xi Liu / Guowei Fu / Ying Chen / Liang Liu /
PubMed AbstractCRISPR-Cas and toxin-antitoxin systems can serve as antiviral defense mechanisms in prokaryotes. In typical toxin-antitoxin systems, toxin activation can limit phage propagation by inducing growth ...CRISPR-Cas and toxin-antitoxin systems can serve as antiviral defense mechanisms in prokaryotes. In typical toxin-antitoxin systems, toxin activation can limit phage propagation by inducing growth arrest or reduced cellular fitness, while the antitoxin neutralizes toxin activity. Here, we study potential functional synergy between a CRISPR-Cas13a system and a type II toxin-antitoxin module (HicAB) from a Leptotrichia bacterium, when heterologously expressed in E. coli, as well as in biochemical and structural analyses. We show that the antitoxin HicB exhibits toxic properties, and Cas13a directly activates HicB, triggering growth inhibition and conferring protection against bacteriophages. Structural analyses reveal that Cas13a binding promotes the spatial proximity of HicB tetramers, likely enabling its activation. The toxin HicA competitively binds to HicB, thereby inhibiting Cas13a-mediated HicB activation. Importantly, both CRISPR RNA and HicB independently suppress HicA toxicity. Structural evidence indicates that CRISPR RNA forms a hetero-tetradecameric complex with HicAB, occluding HicA's active site and neutralizing its toxic function. Thus, our findings indicate functional synergy between distinct bacterial immune strategies.
External linksNat Commun / PubMed:42362581 / PubMed Central
MethodsEM (single particle)
Resolution3.4 Å
Structure data

55261

9svk

EMDB-55261, PDB-9svk:
cryo-EM structure of LwHicAB-crRNA
Method: EM (single particle) / Resolution: 3.4 Å

Source
  • leptotrichia wadei f0279 (bacteria)
KeywordsIMMUNE SYSTEM / toxin-antitoxin / CRISPR RNA binding / prokaryotic immunity

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