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

Laura C Jacques,Aras Kadioglu,Shadia Khandaker,Laura Bricio-Moreno,Christopher G Dowson,Murielle Baltazar,Daniel R Neill,Madikay Senghore,Marie Yang,Dean B Everett,Rong Xu,Stavros Panagiotou

doi:10.1038/s41467-020-15751-6

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.

Highlights

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
BALB/c mice intranasally infected with 106 colony forming units (CFU) of serotype 1 (ST217) displayed 100% mortality within 48 h of infection, compared with 0% mortality in mice infected with the same concentration of serotype 2 (D39) (Fig. 1a)
No bacteria were detectable in the blood of serotype 2 (D39)-infected mice at any time point tested (Fig. 1b). Despite these significant differences in bacteremia, no significant differences in lung bacterial loads were observed between serotype 2 and serotype 1-infected mice over the first 12 h post infection (Fig. 1c) and so we hypothesised that the level of bacterial load in lungs is not directly responsible for bacterial dissemination into the blood stream in this murine model of pneumonia

Summary

Introduction

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. To assess whether high mortality rates in resistant BALB/c mice were unique to serotype 1 (ST217) infection, the pneumonia survival model was repeated with different clinical isolates of S. pneumoniae (Fig. 4a).

Results

Conclusion