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Increased pathogenicity of pneumococcal serotype 1 is driven by rapid autolysis and release of pneumolysin

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Jacques, Laura C., Panagiotou, Stavros, Baltazar, Murielle, Senghore, Madikay, Khandaker, Shadia, Xu, Rong, Bricio-Moreno, Laura, Yang, Marie, Dowson, Christopher G., Everett, Dean B., Neill, Daniel R. and Kadioglu, Aras (2020) Increased pathogenicity of pneumococcal serotype 1 is driven by rapid autolysis and release of pneumolysin. Nature Communications, 11 (1). 1892 . doi:10.1038/s41467-020-15751-6

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Official URL: http://dx.doi.org/10.1038/s41467-020-15751-6

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Abstract

Streptococcus pneumoniae serotype 1 is the predominant cause of invasive pneumococcal disease in sub-Saharan Africa, but the mechanism behind its increased invasiveness is not well understood. Here, we use mouse models of lung infection to identify virulence factors associated with severe bacteraemic pneumonia during serotype-1 (ST217) infection. We use BALB/c mice, which are highly resistant to pneumococcal pneumonia when infected with other serotypes. However, we observe 100% mortality and high levels of bacteraemia within 24 hours when BALB/c mice are intranasally infected with ST217. Serotype 1 produces large quantities of pneumolysin, which is rapidly released due to high levels of bacterial autolysis. This leads to substantial levels of cellular cytotoxicity and breakdown of tight junctions between cells, allowing a route for rapid bacterial dissemination from the respiratory tract into the blood. Thus, our results offer an explanation for the increased invasiveness of serotype 1.

Item Type: Journal Article
Subjects: R Medicine > RC Internal medicine
Divisions: Faculty of Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): Pneumonia, Pneumococcal, Pneumonia, Pneumococcal -- Africa, Sub-Saharan, Lungs -- Infections , Lungs -- Infections -- Africa, Sub-Saharan
Journal or Publication Title: Nature Communications
Publisher: Nature Publishing Group
ISSN: 2041-1723
Official Date: 20 April 2020
Dates:
DateEvent
20 April 2020Published
23 March 2020Accepted
Volume: 11
Number: 1
Article Number: 1892
DOI: 10.1038/s41467-020-15751-6
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
MR/P011284/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
UNSPECIFIEDUniversity Of Liverpoolhttp://dx.doi.org/10.13039/501100000836
UNSPECIFIEDUniversity of Warwickhttp://dx.doi.org/10.13039/501100000741
204457/Z/16/ZWellcome Trusthttp://dx.doi.org/10.13039/100010269
204457/Z/16/ZRoyal Societyhttp://dx.doi.org/10.13039/501100000288

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