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

Author

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  • Laura C. Jacques

    (Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool)

  • Stavros Panagiotou

    (Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool)

  • Murielle Baltazar

    (Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool)

  • Madikay Senghore

    (Medical Research Council Unit, The Gambia)

  • Shadia Khandaker

    (Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool)

  • Rong Xu

    (Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool)

  • Laura Bricio-Moreno

    (Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool)

  • Marie Yang

    (Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool)

  • Christopher G. Dowson

    (School of Life Sciences, University of Warwick)

  • Dean B. Everett

    (Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi, College of Medicine)

  • Daniel R. Neill

    (Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool)

  • Aras Kadioglu

    (Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool)

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.

Suggested Citation

  • 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, 2020. "Increased pathogenicity of pneumococcal serotype 1 is driven by rapid autolysis and release of pneumolysin," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15751-6
    DOI: 10.1038/s41467-020-15751-6
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