{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:13:49Z","timestamp":1789150429730,"version":"build-2803163510"},"reference-count":73,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"37","funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CAREER Award 2237251"],"award-info":[{"award-number":["CAREER Award 2237251"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"publisher","award":["HDTRA1-23-1-0023"],"award-info":[{"award-number":["HDTRA1-23-1-0023"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"NIGMS","doi-asserted-by":"crossref","award":["R35GM143024"],"award-info":[{"award-number":["R35GM143024"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,9,11]]},"abstract":"<jats:p>\n                    Bacteriophage tailspike proteins (TSPs) degrade bacterial capsules to enable infection, yet the molecular determinants of their function and host range remain unclear. We applied deep mutational scanning (DMS) to the endosialidase TSP of\n                    <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                    K1 phage K1F, generating 22,365 single\u2013amino acid variants using an enhanced ORACLE phage engineering platform. Functional scores revealed that the TSP is structurally fragile yet harbors pockets of adaptive flexibility. Mutations within the \u03b2-propeller active site uncovered residues accommodating longer sialic acid chains than captured by structural studies, while the \u03b2 helix stalk emerged as an adaptive \u201ctuning knob\u201d modulating processivity and specificity. Comparative selections across K1 strains identified discrimination hotspots in \u03b2 barrel loops and distal residues outside canonical binding sites, implicating capsule modifications and O-antigen presence as key modulators of host range. By resolving how specific mutations modulate function and host range, this study offers a roadmap for designing phages that overcome capsule-based defenses in pathogenic bacteria.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aed3641","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:58:29Z","timestamp":1789149509000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Mapping structural constraints and adaptive potential in a capsule-degrading phage tailspike protein"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5559-4748","authenticated-orcid":true,"given":"Sarah","family":"Evert","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA."},{"name":"Integrated Program in Biochemistry, University of Wisconsin-Madison, Madison, WI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4064-9333","authenticated-orcid":true,"given":"Phil","family":"Huss","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3718-8364","authenticated-orcid":true,"given":"Dinesh Kumar","family":"Kuppa Baskaran","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA."},{"name":"Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, WI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9584-2491","authenticated-orcid":true,"given":"Karthik","family":"Anantharaman","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2461-1589","authenticated-orcid":true,"given":"Srivatsan","family":"Raman","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA."},{"name":"Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA."},{"name":"Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202012435"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41538-023-00245-8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.11.017"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2020.06.016"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/v16030478"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/v11060567"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0070-8"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2022.102240"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.871855"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2021.06.001"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-81063-4"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41522-024-00497-6"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01945-06"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep15573"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39052-w"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.02949"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46147-5"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.6.2509-2515.2001"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.05304-22"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/Spectrum.01023-21"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2023.08.017"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00455-21"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.01432-23"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1042\/EBC20240015"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.03301"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.00070"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14474"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.02257"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013904"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252312497"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2023.2273567"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2010.01.028"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2020.04.015"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01329-23"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2014.11.002"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03246-21"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2015.07.006"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuab048"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/ve\/veae049"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.63775"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3027"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/10.Supplement_2.S282"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909048720"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.24.8499-8503.2005"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adt6432"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.003970"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.71.8.4872-4874.2005"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M808475200"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1746"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.63.10.4409-4416.1989"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1263\/jbb.101.198"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)61387-0"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M212048200"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02112-21"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.174.23.7757-7761.1992"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.58.2.471-479.1990"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407428102"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-2920.2009.02019.x"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.727847"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1007\/128_2012_349"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00020a019"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21010030"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2021.02.002"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12941-020-00389-5"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2015.08.013"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2006.05158.x"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuz028"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.23.7581-7586.1997"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2014.10.034"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST20230136"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608909103"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00920-21"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty560"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aed3641","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:01:12Z","timestamp":1789149672000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aed3641"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":73,"journal-issue":{"issue":"37","published-print":{"date-parts":[[2026,9,11]]}},"alternative-id":["10.1126\/sciadv.aed3641"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aed3641","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]},"assertion":[{"value":"2025-10-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaed3641"}}