Show simple item record

dc.contributor.authorPanagiotou, Stavros
dc.contributor.authorChaguza, Chrispin
dc.contributor.authorYahya, Reham
dc.contributor.authorAudshasai, Teerawit
dc.contributor.authorBaltazar, Murielle
dc.contributor.authorRessel, Lorenzo
dc.contributor.authorKhandaker, Shadia
dc.contributor.authorAlsahag, Mansoor
dc.contributor.authorMitchell, Tim J.
dc.contributor.authorPrudhomme, Marc
dc.contributor.authorKadioglu, Aras
dc.contributor.authorYang, Marie
dc.date.accessioned2021-10-18T08:42:31Z
dc.date.available2021-10-18T08:42:31Z
dc.date.issued2020-10-14
dc.date.submitted2020-06-09
dc.identifier.others41598-020-73454-w
dc.identifier.other73454
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329485
dc.descriptionFunder: Joint Programming Initiative on Antimicrobial Resistance; doi: http://dx.doi.org/10.13039/100013281
dc.descriptionFunder: UK Medical Research Council
dc.description.abstractAbstract: Streptococcus pneumoniae is a devastating global pathogen. Prevalent in sub-Saharan Africa, pneumococcal serotype 1 is atypical in that it is rarely found as a nasopharyngeal coloniser, yet is described as one of the most common causes of invasive pneumococcal disease. Clonal sequence type (ST)-306 and ST615 are representative of the two major serotype 1 lineages A and C, respectively. Here we investigated the virulence properties and haemolytic activities of these 2 clonal types using in vivo mouse models and in vitro assays. A lethal dose of ST615 administered intranasally to mice led to the rapid onset of disease symptoms and resulted in 90% mortality. In contrast, mice exposed to the same infection dose of ST306 or a pneumolysin (Ply)-deficient ST615 failed to develop any disease symptoms. Interestingly, the 2 strains did not differ in their ability to bind the immune complement or to undergo neutrophil-mediated phagocytosis. Upon comparative genomic analysis, we found higher within-ST sequence diversity in ST615 compared with ST306 and determined that ZmpA, ZmpD proteins, and IgA protease, were uniquely found in ST615. Using cell fractionation and cell contact-dependent assay, we made the unexpected finding that ST615 harbours the expression of two haemolytic variants of Ply: a cell-wall restricted fully haemolytic Ply, and a cytosolic pool of Ply void of any detectable haemolytic activity. This is the first time such a phenomenon has been described. We discuss the biological significance of our observation in relation to the aptitude of the pneumococcus for sustaining its human reservoir.
dc.languageen
dc.publisherNature Publishing Group UK
dc.subjectArticle
dc.subject/692/699
dc.subject/692/699/255
dc.subject/692/699/255/1318
dc.subjectarticle
dc.titleHypervirulent pneumococcal serotype 1 harbours two pneumolysin variants with differential haemolytic activity
dc.typeArticle
dc.date.updated2021-10-18T08:42:30Z
prism.issueIdentifier1
prism.publicationNameScientific Reports
prism.volume10
dc.identifier.doi10.17863/CAM.76933
dcterms.dateAccepted2020-09-14
rioxxterms.versionofrecord10.1038/s41598-020-73454-w
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.identifier.eissn2045-2322


Files in this item

Thumbnail
Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record