Type III CRISPR-Cas provides resistance against nucleus-forming jumbo phages via abortive infection.

Autor:	Mayo-Muñoz D; Department of Microbiology and Immunology, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand; Genetics Otago, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand., Smith LM; Department of Microbiology and Immunology, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand; Genetics Otago, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand., Garcia-Doval C; Department of Biochemistry, University of Zürich 8057, Zürich, Switzerland., Malone LM; Department of Microbiology and Immunology, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand., Harding KR; Department of Microbiology and Immunology, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand; Genetics Otago, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand., Jackson SA; Department of Microbiology and Immunology, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand; Genetics Otago, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand; Bioprotection Aotearoa, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand., Hampton HG; Department of Microbiology and Immunology, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand., Fagerlund RD; Department of Microbiology and Immunology, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand; Genetics Otago, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand; Bioprotection Aotearoa, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand., Gumy LF; Genetics Otago, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand; Department of Anatomy, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand; Brain Health Research Centre, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand., Fineran PC; Department of Microbiology and Immunology, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand; Genetics Otago, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand; Bioprotection Aotearoa, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand. Electronic address: peter.fineran@otago.ac.nz.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2022 Dec 01; Vol. 82 (23), pp. 4471-4486.e9. Date of Electronic Publication: 2022 Nov 16.
DOI:	10.1016/j.molcel.2022.10.028
Abstrakt:	Bacteria have diverse defenses against phages. In response, jumbo phages evade multiple DNA-targeting defenses by protecting their DNA inside a nucleus-like structure. We previously demonstrated that RNA-targeting type III CRISPR-Cas systems provide jumbo phage immunity by recognizing viral mRNA exported from the nucleus for translation. Here, we demonstrate that recognition of phage mRNA by the type III system activates a cyclic triadenylate-dependent accessory nuclease, NucC. Although unable to access phage DNA in the nucleus, NucC degrades the bacterial chromosome, triggers cell death, and disrupts phage replication and maturation. Hence, type-III-mediated jumbo phage immunity occurs via abortive infection, with suppression of the viral epidemic protecting the population. We further show that type III systems targeting jumbo phages have diverse accessory nucleases, including RNases that provide immunity. Our study demonstrates how type III CRISPR-Cas systems overcome the inaccessibility of jumbo phage DNA to provide robust immunity. Competing Interests: Declaration of interests D.M.-M., L.M.S., R.D.F., and P.C.F. are inventors on a filed patent application related to this work. (Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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