{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T01:10:10Z","timestamp":1789002610093,"version":"build-2803163510"},"reference-count":84,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":14,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2021YFA1300901"],"award-info":[{"award-number":["2021YFA1300901"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2022YFA1303500"],"award-info":[{"award-number":["2022YFA1303500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangzhou National Laboratory","award":["GZNL2024A01024"],"award-info":[{"award-number":["GZNL2024A01024"]}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mycobacterium tuberculosis (Mtb) possesses a type III-A CRISPR-Cas system and has anti-plasmid immune activity. However, whether this system exerts other additional functions remains to be characterized. Here, we investigated the in vivo roles of the Mtb CRISPR-Cas system. We show that this system is transcriptionally dependent and exhibits limited ability to counteract exogenous nucleic acids, primarily through the Csm6 protein rather than the Cas10 HD domain. We further demonstrate that this system plays a role in mitigating oxidative stress and antibiotic treatment, a function mainly mediated by the Cas10 HD domain. Importantly, through transposon library screening, we identified oligoribonuclease (Orn) as a regulatory protein of the Mtb CRISPR-Cas system. Deletion of the orn gene resulted in elevated c-di-GMP levels. A subsequent biotin-labeled c-di-GMP pull-down assay identified the transcriptional regulator Rv3058. Knockdown of rv3058 significantly increased cas6 promoter activity, and its transcriptional repressor function was directly modulated by c-di-GMP. This regulatory pathway enhances stress defense by activating multiple protective pathways, including DNA repair, cell envelope maintenance, and iron homeostasis regulation. Together, we conclude that the regulation of the CRISPR-Cas system by Orn-mediated c-di-GMP contributes to oxidative and antibiotic stress responses in Mtb.<\/jats:p>","DOI":"10.1093\/nar\/gkag214","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T12:45:43Z","timestamp":1772109943000},"source":"Crossref","is-referenced-by-count":3,"title":["Orn-mediated c-di-GMP regulates the CRISPR-Cas system to confer stress response in\n                    <i>Mycobacterium tuberculosis<\/i>"],"prefix":"10.1093","volume":"54","author":[{"given":"Wenjing","family":"Yu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071 ,","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing 100049 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisha","family":"Yuan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9508-3598","authenticated-orcid":false,"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071 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Chinese Academy of Sciences , Beijing 100049 ,","place":["China"]},{"name":"State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , Guangzhou 510120 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6153-1348","authenticated-orcid":false,"given":"Yangbo","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0510-1655","authenticated-orcid":false,"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071 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