{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:29:22Z","timestamp":1785421762888,"version":"3.56.0"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"the Project of High-Tech SMES Innovation Improvement of Shandong Province","award":["2025TSGCCZZB0817"],"award-info":[{"award-number":["2025TSGCCZZB0817"]}]},{"name":"the Development Plan of the Youth Innovation Team in Colleges and Universities of Shandong Province","award":["2023KJ355"],"award-info":[{"award-number":["2023KJ355"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2026,7,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Phage-encoded lysins represent a promising class of antimicrobial agents against drug-resistant bacteria due to their ability to degrade bacterial cell walls. This study characterizes a novel prophage-derived lysin, Lys1459, from\n                      <jats:italic toggle=\"yes\">Streptococcus uberis<\/jats:italic>\n                      . We expressed and purified the full-length Lys1459 protein, along with its three individual domains (CHAP, A2, and CBD), to systematically evaluate its antibacterial spectrum, biochemical properties, and therapeutic efficacy. The full-length Lys1459 demonstrated potent lytic activity, achieving a 3-log reduction in\n                      <jats:italic toggle=\"yes\">Streptococcus agalactiae<\/jats:italic>\n                      H-11-1 within 30 min at 50 \u03bcg\/mL in Tris-HCl buffer. Notably, the three functional domains exhibited distinct binding spectra, which collectively contributed to a broad lytic range against streptococcal pathogens, including\n                      <jats:italic toggle=\"yes\">S. agalactiae, S. dysgalactiae, S. uberis<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">S. pyogenes<\/jats:italic>\n                      . In a mouse bacteremia model, intraperitoneal injection of Lys1459 significantly protected mice from lethal infection by\n                      <jats:italic toggle=\"yes\">S. agalactiae<\/jats:italic>\n                      sgcDS001. Furthermore, the bacterial count of\n                      <jats:italic toggle=\"yes\">S. agalactiae<\/jats:italic>\n                      in the blood of the treated mice was reduced by nearly three orders of magnitude. Our findings identify Lys1459 as a triple-binding-domain lysin with broad-spectrum bactericidal activity and robust\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      efficacy, highlighting its potential as a therapeutic alternative against\n                      <jats:italic toggle=\"yes\">S. agalactiae<\/jats:italic>\n                      infections.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      A three-domain lysin, Lys1459, was identified in\n                      <jats:italic toggle=\"yes\">Streptococcus uberis<\/jats:italic>\n                      SX-5-2. The differential binding specificities of the CHAP, A2, and CBD domains to bacterial cells likely underlie the enzyme\u2019s broad-spectrum lytic activity against various\n                      <jats:italic toggle=\"yes\">Streptococcus<\/jats:italic>\n                      species, including\n                      <jats:italic toggle=\"yes\">S. agalactiae<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">S. dysgalactiae<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">S. uberis<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">S. pyogenes.<\/jats:italic>\n                      A significant protective effect against lethal\n                      <jats:italic toggle=\"yes\">S. agalactiae<\/jats:italic>\n                      infection was observed in mice treated intraperitoneally with Lys1459.\n                    <\/jats:p>\n                  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