Anoxia activates CRISPR–Cas immunity in the mouse intestine
The natural context in which CRISPR-Cas systems are active in Enterobacteriaceae has remained enigmatic. Here we find that the Citrobacter rodentium type I-E CRISPR-Cas system is activated by the oxygen-responsive transcriptional regulator Fnr in the anoxic environment of the mouse intestine. Since Fnr-dependent regulation is predicted in ~41% of Enterobacteriaceae cas3 orthologues, we propose that anoxic regulation of CRISPR-Cas immunity is an adaptation that protects Enterobacteriaceae against threats from foreign DNA within the intestinal microbiome.
Authors
- Franz G. Zingl (ORCID: https://orcid.org/0000-0003-0874-4234)
- David W. Basta (ORCID: https://orcid.org/0000-0003-4176-6566)
- Matthew K. Waldor (ORCID: https://orcid.org/0000-0003-1843-7000)
- Sudhir Doranga (ORCID: https://orcid.org/0000-0001-8309-9111)
- Ian W. Campbell (ORCID: https://orcid.org/0000-0003-3019-2560)
- Emily Sullivan (ORCID: https://orcid.org/0000-0001-9558-3883)
Institutions
- Brigham and Women's Hospital (US)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
Publication Details
- Journal
- Nature Microbiology
- Published
- 2025-10-29
- DOI
- https://doi.org/10.1038/s41564-025-02172-8
- Citations
- 2
- Primary Topic
- CRISPR and Genetic Engineering
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- Howard Hughes Medical Institute
- Brigham and Women's Hospital
- Life Sciences Research Foundation
- National Institutes of Health
- Harvard Digestive Diseases Center, Harvard University