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In this study, we isolated and characterized phiK2044, a highly specific and efficient lytic phage targeting the model strain\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      NTUH-K2044. Demonstrating wide host compatibility, potent lytic activity, and robust environmental adaptability, phiK2044 exhibited exceptional efficacy against hypervirulent subtypes, including hypervirulent\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      (45.2%), sequence type 23 (87.5%), and capsular K1 (92.3%). In the mouse model, phiK2044 effectively cleared bacteria without significant side effects, highlighting its therapeutic potential. Mechanistically, we identified\n                      <jats:italic toggle=\"yes\">wcaJ<\/jats:italic>\n                      , a gene encoding a glycosyltransferase essential for capsular synthesis, as the critical determinant of the binding of phiK2044 to the host. Beyond its clinical utility, phiK2044 represents a model for studying phage ecology, host\u2013microbe interactions, and capsule-dependent tropism. Collectively, phiK2044 represents a valuable tool against ST23\/K1\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      infections, such as liver abscesses and bacteremia.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The rise of multidrug-resistant\n                        <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                        demands innovative therapies. This study identifies phiK2044, a lytic phage with high specificity and efficacy against hypervirulent subtypes. It safely clears infections in mice and reveals\n                        <jats:italic toggle=\"yes\">wcaJ<\/jats:italic>\n                        -dependent capsule synthesis as the key host interaction mechanism. Beyond its therapeutic promise, phiK2044 serves as a critical tool for studying phage-host dynamics and capsule-mediated tropism, bridging clinical solutions and fundamental research in combating antimicrobial resistance.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/aem.01380-25","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T15:09:41Z","timestamp":1761923381000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["A capsule-dependent lytic phage for targeting multidrug-resistant and hypervirulent\n                    <i>Klebsiella pneumoniae<\/i>"],"prefix":"10.1128","volume":"91","author":[{"given":"Ziyan","family":"Tian","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00c489v88","id-type":"ROR","asserted-by":"publisher"}],"name":"Capital Institute of Pediatrics, Chinese Academy 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