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bioRxiv · 10.64898/2026.02.24.707460

Structural basis for repurposing a flexible phage tail into an Intraspecific bacterial competition weapon

Yang, F.·Zhang, Z.·Yang, C.·Hou, J.·Feng, H.·Lei, D.·He, Y.-X.
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Abstract

The rise of multidrug-resistant bacteria poses a major threat to human health. Tailocins, which are phage tail-like bacteriocins, offer a way to kill specific bacteria without the risks of horizontal gene transfer found in phage therapy. While the mechanism of contractile R-type tailocins is well-established, the bactericidal action of non-contractile F-type tailocins remains unresolved. Here, we report the high-resolution cryo-EM structure of the F-pyocin from Pseudomonas aeruginosa. The structure reveals a complex nanomachine made of a terminator cap (AlpD/PA0910), a helical tube (PA0633), and a tail tip that mediates a symmetry transition from sixfold to threefold. Notably, the tail tip connects to an elongated central fiber (PA0641) decorated with trimeric side fibers (PA0643/PA0646) involved in host recognition. Through genetic deletion studies and proteomic analysis, we delineate the F-pyocin assembly pathway, establishing that the tape-measure protein (PA0636) serves as a central scaffold coordinating the assembly of the tube, cap, and tail-tip modules. Structural analysis reveals a localized register shift in the central fibers coiled-coil shaft, suggesting a metastable state that may facilitate conformational changes upon host recognition. Our findings detail the atomic structure of an F-type tailocin, uncovering its coordinated assembly pathway and specialized tail-fiber architecture, which establishes a structural framework for engineering next-generation, precision antimicrobials.

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Yang, F., Zhang, Z., Yang, C., Hou, J., Feng, H., Lei, D., He, Y.-X.. 2026-02-24. Structural basis for repurposing a flexible phage tail into an Intraspecific bacterial competition weapon. https://doi.org/10.64898/2026.02.24.707460

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