High-resolution reconstruction of a Jumbo-bacteriophage infecting capsulated bacteria using hyperbranched tail fibers

Ruochen Ouyang, Ana Rita Costa, C. Keith Cassidy, Aleksandra Otwinowska, Vera C. J. Williams, Agnieszka Latka, Phill J. Stansfeld, Zuzanna Drulis-Kawa, Yves Briers, Daniël M. Pelt, Stan J. J. Brouns and Ariane Briegel ()
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Ruochen Ouyang: Xi’an Jiaotong University
Ana Rita Costa: Delft University of Technology
C. Keith Cassidy: University of Oxford
Aleksandra Otwinowska: University of Wroclaw
Vera C. J. Williams: Institute of Biology, Leiden University
Agnieszka Latka: University of Wroclaw
Phill J. Stansfeld: University of Warwick
Zuzanna Drulis-Kawa: University of Wroclaw
Yves Briers: Ghent University
Daniël M. Pelt: Leiden University
Stan J. J. Brouns: Delft University of Technology
Ariane Briegel: Institute of Biology, Leiden University

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract The Klebsiella jumbo myophage ϕKp24 displays an unusually complex arrangement of tail fibers interacting with a host cell. In this study, we combine cryo-electron microscopy methods, protein structure prediction methods, molecular simulations, microbiological and machine learning approaches to explore the capsid, tail, and tail fibers of ϕKp24. We determine the structure of the capsid and tail at 4.1 Å and 3.0 Å resolution. We observe the tail fibers are branched and rearranged dramatically upon cell surface attachment. This complex configuration involves fourteen putative tail fibers with depolymerase activity that provide ϕKp24 with the ability to infect a broad panel of capsular polysaccharide (CPS) types of Klebsiella pneumoniae. Our study provides structural and functional insight into how ϕKp24 adapts to the variable surfaces of capsulated bacterial pathogens, which is useful for the development of phage therapy approaches against pan-drug resistant K. pneumoniae strains.

Date: 2022
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DOI: 10.1038/s41467-022-34972-5

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