Tmn blocks phage spread via plasmolysis and triggers synergistic defence responses
Membrane-associated phage defences remain poorly understood. Here we characterise Tmn, a YobI-family transmembrane P-loop NTPase that protects bacteria from phage infection by establishing a plasmolysis-associated antiviral state. Upon recognising phage T2 RIIB protein, Tmn enhances ATP turnover and selectively exports Mg<sup>2+</sup>, causing rapid cytoplasmic collapse that arrests phage replication without detectable membrane depolarisation or gross leakage of the cell content. Cryo-electron microscopy shows that Tmn assembles into a decameric membrane complex with extended cytosolic arms, an uncommon architecture among P-loop NTPases. The cytosolic arms, including a solenoid-like repeat domain, mediate trigger interaction and determine specificity. In addition to its primary defence function, Tmn-driven ATP collapse activates otherwise silent ATP-depletion-sensing defences, including Gabija and Septu type I, providing a mechanistic basis for synergy among defence systems and limiting secondary phage spread. These findings demonstrate that Tmn is a membrane-integrated sensor-effector that couples phage recognition to metabolic collapse and coordinated multi-layered immunity.
Authors
- Z Zhang
- Franklin L. Nóbrega (ORCID: https://orcid.org/0000-0002-8238-1083)
- Somenath Bakshi (ORCID: https://orcid.org/0000-0003-3864-2546)
- Yi Wu (ORCID: https://orcid.org/0000-0001-5965-0399)
- Ruizhe Li (ORCID: https://orcid.org/0000-0002-9297-7593)
- Emre Gencay Yilmaz
- James A. Milton (ORCID: https://orcid.org/0000-0003-4245-5532)
- Sofya K. Garushyants (ORCID: https://orcid.org/0000-0003-2104-1795)
- Triana Amen (ORCID: https://orcid.org/0000-0003-4808-7806)
- Regan Doherty (ORCID: https://orcid.org/0000-0002-8451-8303)
- Eugene V. Koonin
- Dinshaw J Patel
Institutions
- National Institutes of Health (US)
- Memorial Sloan Kettering Cancer Center (US)
- University of Cambridge (GB)
- United States National Library of Medicine (US)
- University of Southampton (GB)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-03-02
- DOI
- https://doi.org/10.64898/2026.03.01.708804
- Primary Topic
- Bacteriophages and microbial interactions
- Type
- article
- Field-Weighted Citation Impact
- 0.00