TY - JOUR
T1 - High-resolution reconstruction of a Jumbo-bacteriophage infecting capsulated bacteria using hyperbranched tail fibers
AU - Ouyang, Ruochen
AU - Costa, Ana Rita
AU - Cassidy, C. Keith
AU - Otwinowska, Aleksandra
AU - Williams, Vera C.J.
AU - Latka, Agnieszka
AU - Stansfeld, Phill J.
AU - Drulis-Kawa, Zuzanna
AU - Brouns, Stan J.J.
AU - More Authors, null
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85142507754&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-34972-5
DO - 10.1038/s41467-022-34972-5
M3 - Article
AN - SCOPUS:85142507754
SN - 2041-1723
VL - 13
SP - 16
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 7241
ER -