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High-resolution reconstruction of a Jumbo-bacteriophage infecting capsulated bacteria using hyperbranched tail fibers
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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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Highly accurate protein structure prediction with AlphaFold
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Tacconelli, E., Carrara, E., Savoldi, A., Harbarth, S., Mendelson, M., Monnet, D. L., Pulcini, C., Kahlmeter, G., Kluytmans, J., Carmeli, Y., et al. (2018) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(17)30753-3 · Cited by 6,142
Accurate prediction of protein structures and interactions using a 3-track network
Baek, M., DiMaio, F., Anishchenko, I., Dauparas, J., Ovchinnikov, S., Lee, G. R., Wang, J., Cong, Q., Kinch, L. N., Schaeffer, R. D., et al. (2021) · doi:10.1101/2021.06.14.448402 · Cited by 5,549
Potter, S. C., Luciani, A., Eddy, S. R., Park, Y., Lopez, R., & Finn, R. D. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky448 · Cited by 2,607
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Metadata
- Authors
- Ouyang, R., Costa, A. R., Cassidy, C. K., Otwinowska, A., Williams, V. C. J., Latka, A., Stansfeld, P. J., Drulis-Kawa, Z., Briers, Y., Pelt, D. M., Brouns, S. J. J., & Briegel, A.
- Affiliations
- Leiden University (NL)
- Delft University of Technology (NL)
- University of Oxford (GB)
- University of Wrocław (PL)
- Ghent University (BE)
- Corresponding author
- Briegel, Ariane
- ORCID
- Venue
- Nature Communications
- Published
- 2022-11-24
- Volume
- 13
- Issue
- 1
- Pages
- 7241-7241
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC9700779
- OpenAlex
- W4310059371
- Cited by
- 46
- References
- 4
- Citations by year
- 2026: 14 · 2025: 4 · 2024: 17 · 2023: 10 · 2022: 1
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (publishedVersion, cc-by)
- Ghent University Academic Bibliography (Ghent University) (publishedVersion, other-oa)
- Ghent University Academic Bibliography (Ghent University) (publishedVersion)
- Warwick Research Archive Portal (University of Warwick) (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Research Repository (Delft University of Technology) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
- Funders
- Wellcome Trust
- Fonds Wetenschappelijk Onderzoek
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (184.034.014, VI.C.182.027, 016.Veni.192.235, 016.Veni)
- Narodowym Centrum Nauki (UMO-2017/26/M/NZ1/00233, 2020/38/E/NZ8/00432)
- China Scholarship Council (201906280465, 2017-2018)
- Vlaamse regering
- Medical Research Council
- Engineering and Physical Sciences Research Council (EP/R029407/2, EP/R029407/1, 1364172)
- Biotechnology and Biological Sciences Research Council (BB/S003339/1, BB/P01948X/1, BB/P01948X/2)
- H2020 European Research Council (101003229)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Keywords
- bacteriophage structure, capsid structure, phage tail structure, capsular polysaccharide, Klebsiella pneumoniae, phage-host interactions, phage therapy, drug-resistant bacteria
- MeSH terms
- Bacteriophages, Capsid, Klebsiella, Klebsiella pneumoniae, Cryoelectron Microscopy, Capsid Proteins
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