High-resolution reconstruction of a Jumbo-bacteriophage infecting capsulated bacteria using hyperbranched tail fibers
Ruochen Ouyang (Xi’an Jiaotong University, Universiteit Leiden)
Ana Rita Costa (Kavli institute of nanoscience Delft, TU Delft - Applied Sciences)
C. Keith Cassidy (University of Oxford)
Aleksandra Otwinowska (University of Wroclaw)
Vera C.J. Williams (Universiteit Leiden)
Agnieszka Latka (University of Wroclaw, Universiteit Gent)
Phill J. Stansfeld (University of Warwick)
Zuzanna Drulis-Kawa (University of Wroclaw)
Stan J.J. Brouns (TU Delft - Applied Sciences, Kavli institute of nanoscience Delft, TU Delft - Applied Sciences)
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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.
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