Epitopes in the capsular polysaccharide and the porin OmpK36 receptors are required for bacteriophage infection of Klebsiella pneumoniae.

Autor:	Dunstan RA; Centre to Impact AMR, Monash University, Clayton, VIC, Australia; Infection Program, Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia. Electronic address: rhys.dunstan@monash.edu., Bamert RS; Centre to Impact AMR, Monash University, Clayton, VIC, Australia; Infection Program, Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia., Tan KS; Centre to Impact AMR, Monash University, Clayton, VIC, Australia; Infection Program, Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia., Imbulgoda U; Centre to Impact AMR, Monash University, Clayton, VIC, Australia; Infection Program, Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia., Barlow CK; Monash Proteomics & Metabolomics Platform, Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia., Taiaroa G; Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Clayton, VIC, Australia., Pickard DJ; Department of Medicine, University of Cambridge, Cambridge, UK., Schittenhelm RB; Monash Proteomics & Metabolomics Platform, Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia., Dougan G; Department of Medicine, University of Cambridge, Cambridge, UK., Short FL; Centre to Impact AMR, Monash University, Clayton, VIC, Australia; Infection Program, Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia; Department of Medicine, University of Cambridge, Cambridge, UK; Wellcome Sanger Institute, Hinxton, Cambridgeshire, UK., Lithgow T; Centre to Impact AMR, Monash University, Clayton, VIC, Australia; Infection Program, Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia. Electronic address: trevor.lithgow@monash.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Jun 27; Vol. 42 (6), pp. 112551. Date of Electronic Publication: 2023 May 23.
DOI:	10.1016/j.celrep.2023.112551
Abstrakt:	To kill bacteria, bacteriophages (phages) must first bind to a receptor, triggering the release of the phage DNA into the bacterial cell. Many bacteria secrete polysaccharides that had been thought to shield bacterial cells from phage attack. We use a comprehensive genetic screen to distinguish that the capsule is not a shield but is instead a primary receptor enabling phage predation. Screening of a transposon library to select phage-resistant Klebsiella shows that the first receptor-binding event docks to saccharide epitopes in the capsule. We discover a second step of receptor binding, dictated by specific epitopes in an outer membrane protein. This additional and necessary event precedes phage DNA release to establish a productive infection. That such discrete epitopes dictate two essential binding events for phages has profound implications for understanding the evolution of phage resistance and what dictates host range, two issues critically important to translating knowledge of phage biology into phage therapies. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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