{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T06:03:44Z","timestamp":1778047424755,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009016","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T00:00:00Z","timestamp":1607040000000}}],"reference-count":68,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T00:00:00Z","timestamp":1605830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Royal Society Sir Henry Dale Fellowship","award":["204457\/Z\/16\/Z"],"award-info":[{"award-number":["204457\/Z\/16\/Z"]}]},{"name":"Department of Biotechnology, Government of India","award":["BT\/RLF\/Re-entry\/42\/2011"],"award-info":[{"award-number":["BT\/RLF\/Re-entry\/42\/2011"]}]},{"name":"Department of Science & Technology, Government of India","award":["EMR\/2016\/006067"],"award-info":[{"award-number":["EMR\/2016\/006067"]}]},{"name":"Council\u00a0of\u00a0Scientific & Industrial Research, Government of India","award":["27\/0331\/18\/EMR-II"],"award-info":[{"award-number":["27\/0331\/18\/EMR-II"]}]},{"name":"Science and Engineering Research Board, Govternment of India","award":["EMR\/2016\/005909"],"award-info":[{"award-number":["EMR\/2016\/005909"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    The opportunistic pathogen\n                    <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                    has dual lifestyles: one of an asymptomatic colonizer in the human nasopharynx and the other of a deadly pathogen invading sterile host compartments. The latter triggers an overwhelming inflammatory response, partly driven via pore forming activity of the cholesterol dependent cytolysin (CDC), pneumolysin. Although pneumolysin-induced inflammation drives person-to-person transmission from nasopharynx, the primary reservoir for pneumococcus, it also contributes to high mortality rates, creating a bottleneck that hampers widespread bacterial dissemination, thus acting as a double-edged sword. Serotype 1 ST306, a widespread pneumococcal clone, harbours a non-hemolytic variant of pneumolysin (Ply-NH). Performing crystal structure analysis of Ply-NH, we identified Y150H and T172I as key substitutions responsible for loss of its pore forming activity. We uncovered a novel inter-molecular cation-\u03c0 interaction, governing formation of the transmembrane \u03b2-hairpins (TMH) in the pore state of Ply, which can be extended to other CDCs. H150 in Ply-NH disrupts this interaction, while I172 provides structural rigidity to domain-3, through hydrophobic interactions, inhibiting TMH formation. Loss of pore forming activity enabled improved cellular invasion and autophagy evasion, promoting an atypical intracellular lifestyle for pneumococcus, a finding that was corroborated in\n                    <jats:italic>in vivo<\/jats:italic>\n                    infection models. Attenuation of inflammatory responses and tissue damage promoted tolerance of Ply-NH-expressing pneumococcus in the lower respiratory tract. Adoption of this altered lifestyle may be necessary for ST306 due to its limited nasopharyngeal carriage, with Ply-NH, aided partly by loss of its pore forming ability, facilitating a benign association of SPN in an alternative, intracellular host niche.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009016","type":"journal-article","created":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T14:27:10Z","timestamp":1605882430000},"page":"e1009016","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":24,"title":["Structural insights into loss of function of a pore forming toxin and its role in pneumococcal adaptation to an intracellular lifestyle"],"prefix":"10.1371","volume":"16","author":[{"given":"Dilip C.","family":"Badgujar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anjali","family":"Anil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8683-8191","authenticated-orcid":true,"given":"Angharad E.","family":"Green","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manalee Vishnu","family":"Surve","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3693-6279","authenticated-orcid":true,"given":"Shilpa","family":"Madhavan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8377-325X","authenticated-orcid":true,"given":"Alison","family":"Beckett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4055-5161","authenticated-orcid":true,"given":"Ian A.","family":"Prior","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0732-998X","authenticated-orcid":true,"given":"Barsa 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R.","family":"Neill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prasenjit","family":"Bhaumik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4229-5981","authenticated-orcid":true,"given":"Anirban","family":"Banerjee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2020,11,20]]},"reference":[{"issue":"3","key":"ppat.1009016.ref001","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.cell.2017.01.006","article-title":"Pathogen-Mediated Inhibition of Anorexia Promotes Host Survival and Transmission","volume":"168","author":"S Rao","year":"2017","journal-title":"Cell"},{"key":"ppat.1009016.ref002","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.coi.2017.12.003","article-title":"Disease tolerance: concept and 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