{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T13:38:05Z","timestamp":1786541885162,"version":"build-2736575974"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32470190"],"award-info":[{"award-number":["32470190"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,8,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      frequently downregulates or completely loses its capsule. This abolishes infection by capsule-targeting phages but concomitantly may favor infection by phages that exploit non-capsular receptors. Although capsule-targeting mechanisms have been studied in detail, the infection strategies of non-capsular phages remain poorly understood. Here, we analyzed receptor usage across a collection of\n                      <jats:italic toggle=\"yes\">Webervirus<\/jats:italic>\n                      phages and found two contrasting phage-host interaction modes within\n                      <jats:italic toggle=\"yes\">Webervirus<\/jats:italic>\n                      : one group relies on the capsular polysaccharide (CPS) to mediate productive infection, whereas infection by the other group is inhibited by the capsule, compellingly dependence on non-capsular receptors. Genome comparisons revealed a conserved morphogenesis backbone but highly variable receptor-binding protein (RBP) genes among\n                      <jats:italic toggle=\"yes\">Webervirus<\/jats:italic>\n                      phages. These RBPs clustered into distinct clades that correlated with CPS-dependent and non-CPS receptor usage. Within the non-capsular clade, host genetics and complementation established the lipopolysaccharide O-antigen as the required receptor for these phages. Subsequent functional characterization of the RBPs confirmed that this clade specifically targets the O-antigen. Finally, exchanging RBPs by homologous recombination was sufficient to switch receptor usage, and combining phages with distinct receptor usage improved growth suppression in a representative clinical isolate. Together, these results define receptor-linked infection modes within\n                      <jats:italic toggle=\"yes\">Webervirus<\/jats:italic>\n                      and show that RBP variation provides a modular route to diversify host range and increase robustness against capsule-state variability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      is a major multidrug-resistant pathogen, and its frequent capsule loss in clinical settings strongly affects phage therapy outcomes. Our work reveals two contrasting infection modes within\n                      <jats:italic toggle=\"yes\">Webervirus<\/jats:italic>\n                      phages\u2014capsule-dependent versus capsule-inhibited\u2014and links each mode to distinct receptor-binding protein (RBP) clades. By identifying the O-antigen as a key non-capsular receptor, functionally validating O-antigen-targeting RBPs, and showing that RBP exchange can switch receptor usage and that combining complementary phages improves suppression of a clinical isolate, we provide a modular framework for rationally designing phage cocktails that remain effective despite capsule-state variability.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.00046-26","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T12:00:52Z","timestamp":1782129652000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["<i>Webervirus<\/i>\n                    phages exploit capsule- and O-antigen-targeting receptor-binding proteins to access diverse\n                    <i>Klebsiella pneumoniae<\/i>\n                    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