{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T14:44:05Z","timestamp":1791125045311,"version":"4.1.0"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100030888","name":"Fondation priv\u00e9e des H\u00f4pitaux universitaires de Gen\u00e8ve","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100030888","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007636","name":"Fondation Ernst et Lucie Schmidheiny","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007636","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,12,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The rising prevalence of multidrug-resistant\n                      <jats:italic toggle=\"yes\">Klebsiella\n                            pneumoniae<\/jats:italic>\n                      strains, particularly the emerging high-risk ST16\n                        lineage, highlights the urgent need for alternative therapeutic strategies.\n                        A major barrier to effective bacteriophage (phage) therapy against\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      is its polysaccharide capsule, which\n                        hinders phage access to surface receptors. In this study, we identified and\n                        characterized an anti-KL51 capsule depolymerase derived from the anti-ST16\n                        phage PWKp9B. The recombinant DpoK51-9B enzyme was expressed in\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      , purified, and shown to degrade the\n                        KL51 capsule using Percoll density gradient, halo formation on\n                        double-layered-agar, and FITC-dextran exclusion assays. The depolymerase\n                        exhibited strong activity at nanomolar concentrations, retained function up\n                        to 50\u00b0C, and was active only against KL51-positive strains, including\n                        ST16 and ST231 isolates, but not against strains with other capsule types.\n                        Importantly, the depolymerase enabled the lytic activity of the\n                      <jats:italic toggle=\"yes\">Sugarlandvirus<\/jats:italic>\n                      phage GPH82, normally inactive against\n                        encapsulated ST16, demonstrating potent phage-depolymerase synergy. These\n                        findings highlight the potential of recombinant depolymerases to expand\n                        phage host range by unmasking the phage receptors on the surface of the\n                        bacteria and therefore enhance the efficacy of phages against encapsulated\n                        bacteria.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>Bacteriophage therapy and phage-derived therapeutics are attracting\n                            increasing attention as promising alternatives or adjuvants to\n                            antibiotics in the treatment of multidrug-resistant bacterial\n                            infections. Among phage-encoded enzymes, depolymerases are of particular\n                            interest due to their ability to degrade the bacterial polysaccharide\n                            capsule that prevents phage adsorption. Our results highlight the\n                            utility of combining recombinant depolymerases with phages to broaden\n                            their host range and enhance their activity against encapsulated,\n                            drug-resistant pathogens.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.02142-25","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T12:00:33Z","timestamp":1761566433000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Synergistic activity of a KL51-depolymerase and a\n                    <i>Sugarlandvirus<\/i>\n                    bacteriophage against ST16\n                    <i>Klebsiella pneumoniae<\/i>"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6485-8434","authenticated-orcid":true,"given":"M\u00e9lanie","family":"Roch","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01swzsf04","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Molecular Medicine, Medical School, University of Geneva","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8657-1781","authenticated-orcid":true,"given":"Roberto","family":"Sierra","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01swzsf04","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Molecular Medicine, Medical School, University of Geneva","place":["Geneva, Switzerland"]},{"name":"Division of Infectious Diseases, Department of Medicine, Geneva University Hospitals and Medical School","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6926-6224","authenticated-orcid":true,"given":"Ga\u00ebl","family":"Panis","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01swzsf04","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Molecular Medicine, Medical School, University of Geneva","place":["Geneva, Switzerland"]},{"name":"Biomedical Sciences, Faculty of Medicine, University of Geneva","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willames B.","family":"Martins","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Biology Department, University of Oxford","place":["Oxford, United Kingdom"]},{"name":"Ineos Oxford Institute for Antimicrobial Research (IOI)","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Andrey","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01swzsf04","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Molecular Medicine, Medical School, University of Geneva","place":["Geneva, Switzerland"]},{"name":"Division of Infectious Diseases, Department of Medicine, Geneva University Hospitals and Medical School","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","volume-title":"WHO\n                        bacterial priority pathogens list, 2024: bacterial pathogens of public\n                        health importance to guide research, development and strategies to prevent\n                        and control antimicrobial resistance.","author":"World Heath Organization","year":"2024","unstructured":"World Heath Organization. 2024. 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