TY - JOUR
T1 - Increased pathogenicity of pneumococcal serotype 1 is driven by rapid autolysis and release of pneumolysin
AU - Jacques, Laura C.
AU - Panagiotou, Stavros
AU - Baltazar, Murielle
AU - Senghore, Madikay
AU - Khandaker, Shadia
AU - Xu, Rong
AU - Bricio-Moreno, Laura
AU - Yang, Marie
AU - Dowson, Christopher G.
AU - Everett, Dean B.
AU - Neill, Daniel R.
AU - Kadioglu, Aras
N1 - Funding Information:
The study was supported by funding from a UK Medical Research Council Programme Grant (MR/P011284/1) awarded to A.K.; L.C.J. was supported by a University of Liverpool, Institute of Infection and Global Health funded PhD studentship, part funded by the University of Warwick, WCPRS programme. D.R.N. is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant number 204457/Z/16/Z).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85083794976&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-15751-6
DO - 10.1038/s41467-020-15751-6
M3 - Article
C2 - 32312961
AN - SCOPUS:85083794976
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1892
ER -
