Jumbo phage killer immune system targets early infection of nucleus-forming phages
Jumbo bacteriophages of the ϕKZ-like family assemble a lipid-based early phage infection (EPI) vesicle and a proteinaceous nucleus-like structure during infection. These structures protect the phage from nucleases and may create selective pressure for immunity mechanisms targeting this specific phage family. Here, we identify "jumbo phage killer" (Juk), a two-component immune system that terminates infection of ϕKZ-like phages, suppressing the expression of early phage genes and preventing phage DNA replication and phage nucleus assembly while saving the cell. JukA (formerly YaaW) rapidly senses the EPI vesicle by binding to an early-expressed phage protein, gp241, and then directly recruits JukB. The JukB effector structurally resembles a pore-forming toxin and destabilizes the EPI vesicle. Functional anti-ϕKZ JukA homologs are found across bacterial phyla, associated with diverse effectors. These findings reveal a widespread defense system that specifically targets early events executed by ϕKZ-like jumbo phages prior to phage nucleus assembly.
Authors
- Mikhail M. Savitski (ORCID: https://orcid.org/0000-0003-2011-9247)
- Surabhi Hareendranath
- Kira S. Makarova (ORCID: https://orcid.org/0000-0002-8174-2844)
- Karine Lapouge (ORCID: https://orcid.org/0000-0003-0620-9553)
- Jingwen Guan (ORCID: https://orcid.org/0000-0003-1759-2172)
- Eugene V. Koonin (ORCID: https://orcid.org/0000-0003-3943-8299)
- Athanasios Typas (ORCID: https://orcid.org/0000-0002-0797-9018)
- Isabelle Becher (ORCID: https://orcid.org/0000-0001-7170-2235)
- Kim Remans (ORCID: https://orcid.org/0000-0002-4394-7953)
- Frank Stein (ORCID: https://orcid.org/0000-0001-9695-1692)
- Xueli Cao (ORCID: https://orcid.org/0000-0001-9160-1511)
- Yue Feng (ORCID: https://orcid.org/0000-0002-1576-1385)
- David A. Agard (ORCID: https://orcid.org/0000-0003-3512-695X)
- Joseph Bondy‐Denomy (ORCID: https://orcid.org/0000-0002-4909-9481)
- Yuping Li (ORCID: https://orcid.org/0000-0003-2057-3271)
- Linlin Guan
- Siqi Yang (ORCID: https://orcid.org/0000-0002-7760-9856)
- Arne Boergel
Institutions
- National Institutes of Health (US)
- University of California, San Francisco (US)
- Chan Zuckerberg Initiative (United States) (US)
- European Molecular Biology Laboratory (DE)
- Beijing University of Chemical Technology (CN)
Publication Details
- Journal
- Cell
- Published
- 2025-03-19
- DOI
- https://doi.org/10.1016/j.cell.2025.02.016
- Citations
- 19
- Primary Topic
- Bacteriophages and microbial interactions
- Type
- article
- Field-Weighted Citation Impact
- 32.61
Funders
- Foundation for the National Institutes of Health