{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:13:27Z","timestamp":1792858407034,"version":"4.5.0"},"reference-count":108,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/X009130\/1"],"award-info":[{"award-number":["MR\/X009130\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Rosetrees Trust and Stoneygate Trust","award":["100275"],"award-info":[{"award-number":["100275"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>\n                      <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                    <\/jats:italic>\n                    (the pneumococcus) causes a range of life-threatening diseases including pneumonia, sepsis and meningitis. Despite widespread vaccine deployment, pneumococcal disease remains a leading cause of global mortality. The human nasopharynx is its principal ecological niche, and all pneumococcal disease originates from this reservoir of organisms. Acute infections are, however, an evolutionary dead-end for the pneumococcus. What sustains the pneumococcus within human populations are cycles of colonisation and transmission. To persist within the nasopharynx, it must overcome the physical and immunological barriers established by the host while acquiring sufficient nutrients to proliferate in the face of competing airway microbes. Here, we outline the metabolic, microbial, and immunological challenges of colonisation, and the often-competing demands of transmission, which together have shaped the pneumococcus into one of the most formidable human pathogens.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013675","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T18:31:03Z","timestamp":1763058663000},"page":"e1013675","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["The metabolic, microbial and immunological demands of pneumococcal colonisation"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7911-8153","authenticated-orcid":true,"given":"Daniel R.","family":"Neill","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9997-9532","authenticated-orcid":true,"given":"Thomas B.","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"issue":"2","key":"ppat.1013675.ref001","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/S0002-9343(88)80334-6","article-title":"Progressive disseminated histoplasmosis in patients with acquired immunodeficiency syndrome","volume":"85","author":"PC Johnson","year":"1988","journal-title":"Am J Med"},{"key":"ppat.1013675.ref002","doi-asserted-by":"crossref","first-page":"587730","DOI":"10.3389\/fped.2020.587730","article-title":"Carriage dynamics of pneumococcal serotypes in naturally colonized infants in a rural African setting during the first year of life","volume":"8","author":"C Chaguza","year":"2021","journal-title":"Front Pediatr"},{"issue":"9","key":"ppat.1013675.ref003","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1093\/infdis\/jiaa558","article-title":"Dynamics of pneumococcal carriage in adults: a new look at an old paradigm","volume":"223","author":"ST Almeida","year":"2021","journal-title":"J Infect Dis"},{"issue":"1","key":"ppat.1013675.ref004","doi-asserted-by":"crossref","first-page":"12497","DOI":"10.1038\/s41598-018-30345-5","article-title":"Longitudinal characterization of nasopharyngeal colonization with Streptococcus pneumoniae in a South African birth cohort post 13-valent pneumococcal conjugate vaccine implementation","volume":"8","author":"FS Dube","year":"2018","journal-title":"Sci Rep"},{"issue":"3","key":"ppat.1013675.ref005","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.tim.2012.11.005","article-title":"Influence of bacterial interactions on pneumococcal colonization of the 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Ganaie","year":"2020","journal-title":"mBio"},{"issue":"3","key":"ppat.1013675.ref009","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1128\/CMR.00024-15","article-title":"Pneumococcal capsules and their types: past, present, and future","volume":"28","author":"KA Geno","year":"2015","journal-title":"Clin Microbiol Rev"},{"issue":"1","key":"ppat.1013675.ref010","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1128\/IAI.01475-06","article-title":"Capsule enhances pneumococcal colonization by limiting mucus-mediated clearance","volume":"75","author":"AL Nelson","year":"2007","journal-title":"Infect Immun"},{"issue":"4","key":"ppat.1013675.ref011","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1009158","article-title":"Neuraminidase B controls neuraminidase A-dependent mucus production and evasion","volume":"17","author":"AJ Hammond","year":"2021","journal-title":"PLoS 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Apte","year":"2025","journal-title":"PLoS Pathog"},{"issue":"3","key":"ppat.1013675.ref027","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.chom.2016.07.019","article-title":"Streptococcus pneumoniae senses a human-like sialic acid profile via the response regulator CiaR","volume":"20","author":"K Hentrich","year":"2016","journal-title":"Cell Host Microbe"},{"issue":"1","key":"ppat.1013675.ref028","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1600-065X.2011.01039.x","article-title":"Intracellular sensors of extracellular bacteria","volume":"243","author":"TB Clarke","year":"2011","journal-title":"Immunol Rev"},{"issue":"4","key":"ppat.1013675.ref029","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1111\/j.1462-5822.2011.01746.x","article-title":"Recognition of Streptococcus pneumoniae by the innate immune system","volume":"14","author":"U Koppe","year":"2012","journal-title":"Cell 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Oliver","year":"2019","journal-title":"Clin Exp Immunol"},{"issue":"8","key":"ppat.1013675.ref039","doi-asserted-by":"crossref","DOI":"10.1016\/j.cmi.2016.05.017","article-title":"A dynamic relationship between mucosal T helper type 17 and regulatory T-cell populations in nasopharynx evolves with age and associates with the clearance of pneumococcal carriage in humans","volume":"22","author":"A Mubarak","year":"2016","journal-title":"Clin Microbiol Infect"},{"issue":"4","key":"ppat.1013675.ref040","article-title":"Human nasal challenge with Streptococcus pneumoniae is immunising in the absence of carriage","volume":"8","author":"AKA Wright","year":"2012","journal-title":"PLoS Pathog"},{"issue":"10","key":"ppat.1013675.ref041","doi-asserted-by":"crossref","first-page":"4523","DOI":"10.1172\/JCI128865","article-title":"Innate and adaptive nasal mucosal immune responses following experimental human pneumococcal colonization","volume":"129","author":"SP Jochems","year":"2019","journal-title":"J Clin Invest"},{"issue":"9","key":"ppat.1013675.ref042","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1038\/s41590-019-0444-8","article-title":"The biology and functional importance of MAIT cells","volume":"20","author":"DI Godfrey","year":"2019","journal-title":"Nat Immunol"},{"issue":"10","key":"ppat.1013675.ref043","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1164\/rccm.201401-0128OC","article-title":"Density and duration of pneumococcal carriage is maintained by transforming growth factor \u03b21 and T regulatory cells","volume":"189","author":"DR Neill","year":"2014","journal-title":"Am J Respir Crit Care Med"},{"key":"ppat.1013675.ref044","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.3389\/fmicb.2020.01543","article-title":"Pneumolysin: pathogenesis and therapeutic target","volume":"11","author":"AT Nishimoto","year":"2020","journal-title":"Front 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profiling","volume":"287","author":"T H\u00e4rtel","year":"2012","journal-title":"J Biol Chem"},{"issue":"19","key":"ppat.1013675.ref051","doi-asserted-by":"crossref","first-page":"5709","DOI":"10.1128\/JB.183.19.5709-5717.2001","article-title":"Genome of the bacterium Streptococcus pneumoniae strain R6","volume":"183","author":"J Hoskins","year":"2001","journal-title":"J Bacteriol"},{"issue":"6","key":"ppat.1013675.ref052","doi-asserted-by":"crossref","DOI":"10.1093\/femspd\/ftaa051","article-title":"A systematic strategy using a reconstructed genome-scale metabolic network for pathogen Streptococcus pneumoniae D39 to find novel potential drug targets","volume":"78","author":"N Pedram","year":"2020","journal-title":"Pathog Dis"},{"issue":"23","key":"ppat.1013675.ref053","doi-asserted-by":"crossref","first-page":"3865","DOI":"10.1002\/1873-3468.13045","article-title":"Glycan-metabolizing enzymes in microbe-host interactions: the Streptococcus pneumoniae 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