Hypervirulent pneumococcal serotype 1 harbours two pneumolysin variants with differential haemolytic activity
dc.contributor.author | Panagiotou, Stavros | |
dc.contributor.author | Chaguza, Chrispin | |
dc.contributor.author | Yahya, Reham | |
dc.contributor.author | Audshasai, Teerawit | |
dc.contributor.author | Baltazar, Murielle | |
dc.contributor.author | Ressel, Lorenzo | |
dc.contributor.author | Khandaker, Shadia | |
dc.contributor.author | Alsahag, Mansoor | |
dc.contributor.author | Mitchell, Tim J. | |
dc.contributor.author | Prudhomme, Marc | |
dc.contributor.author | Kadioglu, Aras | |
dc.contributor.author | Yang, Marie | |
dc.date.accessioned | 2021-10-18T08:42:31Z | |
dc.date.available | 2021-10-18T08:42:31Z | |
dc.date.issued | 2020-10-14 | |
dc.date.submitted | 2020-06-09 | |
dc.date.updated | 2021-10-18T08:42:30Z | |
dc.description | Funder: Joint Programming Initiative on Antimicrobial Resistance; doi: http://dx.doi.org/10.13039/100013281 | |
dc.description | Funder: UK Medical Research Council | |
dc.description.abstract | Abstract: 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.identifier.doi | 10.17863/CAM.76933 | |
dc.identifier.eissn | 2045-2322 | |
dc.identifier.other | s41598-020-73454-w | |
dc.identifier.other | 73454 | |
dc.identifier.uri | https://www.repository.cam.ac.uk/handle/1810/329485 | |
dc.language | en | |
dc.publisher | Nature Publishing Group UK | |
dc.subject | Article | |
dc.subject | /692/699 | |
dc.subject | /692/699/255 | |
dc.subject | /692/699/255/1318 | |
dc.subject | article | |
dc.title | Hypervirulent pneumococcal serotype 1 harbours two pneumolysin variants with differential haemolytic activity | |
dc.type | Article | |
dcterms.dateAccepted | 2020-09-14 | |
prism.issueIdentifier | 1 | |
prism.publicationName | Scientific Reports | |
prism.volume | 10 | |
rioxxterms.licenseref.uri | http://creativecommons.org/licenses/by/4.0/ | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1038/s41598-020-73454-w |
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