{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:20:23Z","timestamp":1792790423525,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,30]]},"group-title":"Microbiology","reference-count":103,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NIAID","award":["R01AI195985"],"award-info":[{"award-number":["R01AI195985"]}]},{"name":"NIH","award":["R35GM142924"],"award-info":[{"award-number":["R35GM142924"]}]},{"name":"Gates Foundation","award":["OPP1034556"],"award-info":[{"award-number":["OPP1034556"]}],"id":[{"id":"https:\/\/ror.org\/0456r8d26","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Wellcome Trust","award":["098051"],"award-info":[{"award-number":["098051"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Wellcome Trust","award":["206194"],"award-info":[{"award-number":["206194"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute for Health and Care Research","id":[{"id":"https:\/\/ror.org\/0187kwz08","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Exchange of genetic loci encoding extracellular capsular polysaccharides in bacteria can change capsular antigens or serotype, which, in turn, can lead to evasion of vaccines targeting the capsule. However, the evolutionary dynamics and drivers of bacterial capsule switching remain poorly understood. Here, we investigate the evolutionary dynamics and correlates of capsule switching in bacteria, using the human-restricted bacterial pathogen\n                  <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                  as an example, using 10,558 genetically and geographically diverse whole-genome sequences. Our phylogenomic and ancestral state reconstruction analysis revealed that the propensity for capsule switching varies by capsule type and genetic background. We found capsule switches only between \u223c4% of all possible capsule-type pairs, varying by specific pairs and switching direction. We also found associations between capsule switching patterns and genetic and ecological factors, including nasopharyngeal carriage duration, capsule biosynthesis locus size, and capsule thickness. Furthermore, the genetic similarity of the replacing and replaced capsule loci was primarily associated with the frequency of switching between specific capsule type pairs. Although a few specific non-capsule genomic loci were associated with the propensity for capsule switching across distinct lineages, the collective effect of the genetic background appears to influence capsule switching more strongly. These findings shed light on how bacterial capsule types and lineages undergo capsule switching influenced by genetic and ecological factors, informing our understanding of the emergence of novel capsule-genotype combinations that may impact the design of capsule-targeting glycoconjugate vaccines.\n                <\/jats:p>","DOI":"10.64898\/2026.09.24.752487","type":"posted-content","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:40:22Z","timestamp":1790790022000},"source":"Crossref","is-referenced-by-count":0,"title":["The global evolutionary dynamics of natural capsule switching in a human-restricted bacterial pathogen"],"prefix":"10.64898","author":[{"given":"Chrispin","family":"Chaguza","sequence":"first","affiliation":[{"name":"Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, USA"},{"name":"Department of Host-Microbe Interactions, St Jude Children\u2019s Research Hospital, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"York","sequence":"additional","affiliation":[{"name":"Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2182-0222","authenticated-orcid":false,"given":"Stephanie W.","family":"Lo","sequence":"additional","affiliation":[{"name":"Parasites and Microbes Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, United Kingdom"},{"name":"Milner Centre for Evolution, Life Sciences Department, University of Bath, Bath, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akuzike","family":"Kalizang\u2019oma","sequence":"additional","affiliation":[{"name":"Malawi-Liverpool-Wellcome-Trust Clinical Research Programme, Blantyre, Malawi"},{"name":"Research Department of Infection, Division of Infection and Immunity, University College London, London, UK"},{"name":"Department of Pathology, School of Medicine and Oral Health, Kamuzu University of Health Sciences, Blantyre, Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca A.","family":"Gladstone","sequence":"additional","affiliation":[{"name":"Parasites and Microbes Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, United Kingdom"},{"name":"Department of Biostatistics, Faculty of Medicine, University of Oslo, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda A.","family":"Kwambana-Adams","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory","family":"Cave","sequence":"additional","affiliation":[{"name":"Research Department of Infection, Division of Infection and Immunity, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Global Pneumococcal Sequencing (GPS) consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith P.","family":"Klugman","sequence":"additional","affiliation":[{"name":"Pneumonia and Pandemic Preparedness, Global Health Division, Bill & Melinda Gates Foundation, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl P.","family":"Andam","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University at Albany, State University of New York, Albany, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S.","family":"Heyderman","sequence":"additional","affiliation":[{"name":"Research Department of Infection, Division of Infection and Immunity, University College London, London, 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