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

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

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)
22 Downloads (Pure)

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.

Original languageEnglish
Article number1892
Number of pages13
JournalNature Communications
Volume11
Early online date20 Apr 2020
DOIs
Publication statusPublished - 2020

Keywords

  • Bacterial pathogenesis
  • Bacterial toxins
  • Bacteriology
  • Infection

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General
  • General Physics and Astronomy

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