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Defending in the membrane: Mechanistic insights into Kiwa and Tmn phage defense systems
Bacteria and archaea have evolved a vast arsenal of defence mechanisms to counteract viral infection, yet many remain poorly understood. While most well-characterised systems operate in the cytoplasm, an emerging class of membrane-associated defences provides a first line of protection at the primary site of phage entry. Here, we characterise two distinct membrane-associated defence systems, Kiwa and Tmn, which employ fundamentally different strategies to disrupt phage infection.
The Kiwa system is a large membrane-associated supercomplex composed of KwaA tetramers and KwaB dimers. It senses membrane perturbations induced by phage infection, activating an antiviral response. Upon activation, KwaB binds ejected phage DNA through its DUF4868 domain, stalling replication forks and interfering with late transcription. We also identify an unexpected coordination between Kiwa and RecBCD, mediated by the phage-encoded Gam protein, which can inhibit both systems but not simultaneously, as binding to one precludes inhibition of the other.
In contrast, the Tmn system consists of a transmembrane decamer that is directly activated by phage proteins such as T2 RIIB. Upon activation, Tmn drives ion export, inducing plasmolysis. This osmotic imbalance halts phage maturation, effectively stalling infection. Together, these findings highlight membrane-associated defence systems as a critical yet underexplored facet of bacterial immunity. By targeting different stages of phage infection, Kiwa and Tmn exemplify the diverse strategies bacteria employ at the membrane interface.
Date:
24 November 2025, 11:00
Venue:
Dorothy Crowfoot Hodgkin Building, off South Parks Road OX1 3QU
Venue Details:
Seminar Room 2, Room 20-138
Speaker:
Associate Professor Franklin L Nobrega (University of Southampton)
Organising department:
Department of Biochemistry
Organisers:
Associate Professor Dmitry Ghilarov (Department of Biochemistry, Oxford University),
Professor Tobias Warnecke (Department of Biochemistry, Oxford University)
Organiser contact email address:
dmitry.ghilarov@bioch.ox.ac.uk
Hosts:
Associate Professor Dmitry Ghilarov (Department of Biochemistry, Oxford University),
Professor Tobias Warnecke (Dept. of Biochemistry, University of Oxford)
Part of:
Microbiology and Systems Biology (MSB) seminars, Department of Biochemistry
Booking required?:
Not required
Audience:
Members of the University only
Editors:
Sarah-Jane Scard,
Jessica Barnes
