Background

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.

Methods

To identify factors that make key contributions to serotype-1 disease pathogenesis, we used a BALB/c model of pneumococcal pneumonia. Disease severity of infection with African serotype-1 (ST217 and ST3081) was compared to serotypes 2 (D39), 5, 6B and 7F.

Results

BALB/c mice are normally highly resistant to pneumococcal pneumonia with little to no bacterial dissemination from lungs into the bloodstream, resulting in 100% survival rates. However, when BALB/c mice were intranasally infected with serotype-1 ST217, 100% mortality was observed with high levels of bacteraemia within 24 hours. Mice challenged with all other serotypes survived.

We show that serotype-1 produces pneumolysin in large quantities, rapidly released due to high levels of bacterial autolysis. This released pneumolysin induces substantial levels of cellular cytotoxicity and breakdown of tight junctions between cells, allowing a route for rapid bacterial dissemination from the respiratory tract into blood; offering an explanation for increased serotype-1 invasiveness.

Conclusions

In conclusion, serotype-1 virulence was driven by rapid bacterial autolysis, which led to the release of large quantities of pneumolysin, enabling rapid bacterial dissemination into the bloodstream.

Background

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.

Methods

To identify factors that make key contributions to serotype-1 disease pathogenesis, we used a BALB/c model of pneumococcal pneumonia. Disease severity of infection with African serotype-1 (ST217 and ST3081) was compared to serotypes 2 (D39), 5, 6B and 7F.

Results

BALB/c mice are normally highly resistant to pneumococcal pneumonia with little to no bacterial dissemination from lungs into the bloodstream, resulting in 100% survival rates. However, when BALB/c mice were intranasally infected with serotype-1 ST217, 100% mortality was observed with high levels of bacteraemia within 24 hours. Mice challenged with all other serotypes survived.

We show that serotype-1 produces pneumolysin in large quantities, rapidly released due to high levels of bacterial autolysis. This released pneumolysin induces substantial levels of cellular cytotoxicity and breakdown of tight junctions between cells, allowing a route for rapid bacterial dissemination from the respiratory tract into blood; offering an explanation for increased serotype-1 invasiveness.

Conclusions

In conclusion, serotype-1 virulence was driven by rapid bacterial autolysis, which led to the release of large quantities of pneumolysin, enabling rapid bacterial dissemination into the bloodstream.