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While artificial intelligence (AI) has recently boosted phenotype\u2010based repurposing of drugs for other human pathogens, this remains to be investigated for\n                    <jats:italic>S. pneumoniae<\/jats:italic>\n                    . Thus, we leveraged ensembles of transformer, graph, and tree models, each trained on a set of 1849 actives along with 34\u00a0503 inactives, to prospectively examine 6747 drugs. Of 11 selected candidate antibiotics, nine were found to strongly reduce in vitro growth of\n                    <jats:italic>S. pneumoniae<\/jats:italic>\n                    R6, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of \u2264 0.4\u00a0\u00b5g\/mL. The most potent drugs, thiostrepton and ceftiofur, had IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 0.0001\u00a0\u00b5g\/mL (60.1 pM) and 0.0004\u00a0\u00b5g\/mL (764\u00a0pM), respectively. Thiostrepton remained highly potent even against multidrug\u2010resistant strains, suggesting it could be effectively deployed to treat common non\u2010invasive\n                    <jats:italic>S. pneumoniae<\/jats:italic>\n                    infection as part of antibiotic stewardship efforts.\n                  <\/jats:p>","DOI":"10.1002\/advs.76959","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:01:25Z","timestamp":1789542085000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Artificial Intelligence\u2010Guided Phenotypic Drug Repurposing Against\n                    <i>Streptococcus pneumoniae<\/i>"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5924-2306","authenticated-orcid":false,"given":"Joshua S.","family":"Fitch","sequence":"first","affiliation":[{"name":"Imperial College London Department of Bioengineering Sir Michael Uren Hub White City campus  London UK"},{"name":"MRC Centre for Global Infectious Disease Analysis School of Public Health Sir Michael Uren Hub White City campus  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad D.","family":"Ariadi","sequence":"additional","affiliation":[{"name":"Imperial College London Department of Bioengineering Sir Michael Uren Hub White City campus  London UK"},{"name":"Imperial College London Department of Chemistry Molecular Sciences Research Hub White City campus  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1771-6913","authenticated-orcid":false,"given":"Min Jung","family":"Kwun","sequence":"additional","affiliation":[{"name":"MRC Centre for Global Infectious Disease Analysis School of Public Health Sir Michael Uren Hub White City campus  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie","family":"Howells","sequence":"additional","affiliation":[{"name":"MRC Centre for Global Infectious Disease Analysis School of Public Health Sir Michael Uren Hub White City campus  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saiveth","family":"Hernandez\u2010Hernandez","sequence":"additional","affiliation":[{"name":"Inserm UMR 1307 CRCI2NA Nantes Universit\u00e9  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6303-8768","authenticated-orcid":false,"given":"Nicholas J.","family":"Croucher","sequence":"additional","affiliation":[{"name":"MRC Centre for Global Infectious Disease Analysis School of Public Health Sir Michael Uren Hub White City campus  London UK"},{"name":"Parasites &amp; Microbes programme Wellcome Sanger Institute Wellcome Genome Campus  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4078-743X","authenticated-orcid":false,"given":"Pedro J.","family":"Ballester","sequence":"additional","affiliation":[{"name":"Imperial College London Department of Bioengineering Sir Michael Uren Hub White City campus  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Drug\u2010Resistant Infections: A Threat to Our Economic Future (Vol. 2): Final Report","author":"Jonas O. 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