View the Current Issue

Article

  • The EMBO Journal (2004) 23, 2166 - 2174
  • doi:10.1038/sj.emboj.7600214

Published online: 22 April 2004

Interactions with fibronectin attenuate the virulence of Streptococcus pyogenes

Patrik Nyberg1,4, Takao Sakai2,4, Kyu Hong Cho3, Michael G Caparon3, Reinhard Fässler2 and Lars Björck1

  1. Department of Cell and Molecular Biology, Section for Molecular Pathogenesis, Lund University, Lund, Sweden
  2. Department of Molecular Medicine, Max Planck Institute for Biochemistry, Martinsried, Germany
  3. Department of Molecular Microbiology, Center for Infectious Disease Research, Washington University School of Medicine, St Louis, MO, USA
  4. These authors contributed equally to this study

Correspondence to:

Patrik Nyberg, Section for Molecular Pathogenesis, Department of Cell and Molecular Biology, Lund University, BMC, B14, 22184 Lund, Sweden. Tel.: +46 46 222 4489; Fax: +46 46 157 756; E-mail: patrik.nyberg@medkem.lu.se

Received 23 June 2003; Accepted 25 March 2004

Fibronectin-binding surface proteins are found in many bacterial species. Most strains of Streptococcus pyogenes, a major human pathogen, express the fibronectin-binding protein F1, which promotes bacterial adherence to and entry into human cells. In this study, the role of fibronectin in S. pyogenes virulence was investigated by introducing the protein F1 gene in an S. pyogenes strain lacking this gene. Furthermore, transgenic mice lacking plasma fibronectin were used to examine the relative contribution of plasma and cellular fibronectin to S. pyogenes virulence. Unexpectedly, protein F1-expressing bacteria were less virulent to normal mice, and virulence was partly restored when these bacteria were used to infect mice lacking plasma fibronectin. Dissemination to the spleen of infected mice was less efficient for fibronectin-binding bacteria. These bacteria also disseminated more efficiently in mice lacking plasma fibronectin, demonstrating that plasma fibronectin bound to the bacterial surface downregulates S. pyogenes virulence by limiting bacterial spread. From an evolutionary point of view, these results suggest that reducing virulence by binding fibronectin adds selective advantages to the bacterium.

  • Keywords:

    • adherence,
    • fibronectin,
    • internalisation,
    • S. pyogenes,
    • virulence