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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.
The mechanisms behind the high invasiveness of Streptococcus pneumoniae serotype 1 are unclear. Here, Jacques et al. show that this feature is due to overproduction and rapid release of pneumolysin, which induces cytotoxicity and breakdown of tight junctions, allowing rapid bacterial dissemination from the respiratory tract into the blood.
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1 Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK (GRID:grid.10025.36) (ISNI:0000 0004 1936 8470)
2 Medical Research Council Unit, The Gambia, Bakau, Gambia (GRID:grid.415063.5) (ISNI:0000 0004 0606 294X)
3 School of Life Sciences, University of Warwick, Warwick, UK (GRID:grid.7372.1) (ISNI:0000 0000 8809 1613)
4 Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi, College of Medicine, Blantyre, Malawi (GRID:grid.419393.5)