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A Tripartite Co-culture System Reveals Defensive Mutualism Between a Nanobdellati Symbiont and Its Host

Preprint Created on 05 Jun 2026 bioRxiv

Archaeal symbioses remain among the least understood cellular interactions. Ultra-small Nanobdellati (initially called DPANN) archaea rely on larger hosts for survival, yet their effects on host eco-physiology and their interactions with infecting viruses have not yet been examined experimentally. Here, we established the first stable tripartite co-culture comprising a Nanobdellales symbiont (YN4), its archaeal host (YN4HA), and a virus (MTIV4). We analyzed this system using physiological, genomic, transcriptomic, glycoproteomic, and cryo-electron tomography (cryoET) approaches. CryoET analysis revealed that the Nanobdellales archaeon formed cone-like structures to contact the host, as has been observed in other Nanobdellati-host systems. In this system, the host is infected by the virus. The Nanobdellales archaeon mitigated virus-induced growth inhibition of the host without any detectable fitness cost, indicating a defensive mutualism rather than a strictly parasitic relationship. This protective effect may involve Nanobdellati-driven remodeling of host cell surface glycans, suggesting a previously unrecognized glycan-mediated defense strategy. Overall, our tripartite system provides new insight into complex archaeal interactions in extreme environments that cannot be captured through conventional binary co-culture systems.

Sakai, H. D., Schwarzer, S., Nakagawa, S., Reyhani, M., Shimamura, S., Johnson, M. D., Tsukamoto, Y., Shimizu, M., Takai, K., Nunoura, T., Kurosawa, N., Ohkuma, M., Hackl, T., Ghosal, D., Quax, T. E. F.

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