@article{c54f8d0856e34a8d94931ac1caf04832,
title = "Epitopes in the capsular polysaccharide and the porin OmpK36 receptors are required for bacteriophage infection of Klebsiella pneumoniae",
abstract = "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.",
keywords = "CP: Microbiology",
author = "Dunstan, {Rhys A.} and Bamert, {Rebecca S.} and Tan, {Kher Shing} and Uvini Imbulgoda and Barlow, {Christopher K.} and George Taiaroa and Pickard, {Derek J.} and Schittenhelm, {Ralf B.} and Gordon Dougan and Short, {Francesca L.} and Trevor Lithgow",
note = "Funding Information: We thank Professor Richard Strugnell for the Klebsiella strains used in this study and expert advice on Klebsiella capsule polysaccharides and Dr. Kelly Wyres for providing expert advice and unpublished data on the genome sequence verifications of these strains. Research was supported by NHMRC Investigator Grant 2016330 from the National Health and Medical Research Council of Australia (NHMRC) and by DP220100338 from the Australian Research Council (ARC). F.L.S. was a Sir Henry Wellcome Fellow (106063/A/14/Z). OmpK37 antibody production was performed at the Monash Animal Research Platform (MARP) and covered by ERM project #14152 (MARP2/2016/147). R.A.D. R.S.B. K.S.T. U.I. and G.T. performed biological experiments. F.L.S. performed TraDIS data analysis. C.K.B. performed and analyzed the capsule LC-MS experiments. T.L. D.J.P. G.D. and R.B.S. supervised the project. R.A.D. and T.L. wrote the paper. All authors analyzed data and contributed critical evaluation to the final version of the manuscript. The authors declare no competing interests. Funding Information: We thank Professor Richard Strugnell for the Klebsiella strains used in this study and expert advice on Klebsiella capsule polysaccharides and Dr. Kelly Wyres for providing expert advice and unpublished data on the genome sequence verifications of these strains. Research was supported by NHMRC Investigator Grant 2016330 from the National Health and Medical Research Council of Australia (NHMRC) and by DP220100338 from the Australian Research Council (ARC). F.L.S. was a Sir Henry Wellcome Fellow ( 106063/A/14/Z ). OmpK37 antibody production was performed at the Monash Animal Research Platform (MARP) and covered by ERM project #14152 ( MARP2/2016/147 ). Publisher Copyright: {\textcopyright} 2023 The Author(s)",
year = "2023",
month = jun,
day = "27",
doi = "10.1016/j.celrep.2023.112551",
language = "English",
volume = "42",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Elsevier",
number = "6",
}