Human-specific staphylococcal virulence factors enhance pathogenicity in a humanised zebrafish C5a receptor model

Kyle D. Buchan, Michiel van Gent, Tomasz K. Prajsnar, Nikolay V. Ogryzko, Nienke W.M. de Jong, Julia Kolata, Simon J. Foster, Jos A.G. van Strijp, Stephen A. Renshaw

Research output: Contribution to journalArticlepeer-review

Abstract

Staphylococcus aureus infects ∼30% of the human population and causes a spectrum of pathologies ranging from mild skin infections to life-threatening invasive diseases. The strict host specificity of its virulence factors has severely limited the accuracy of in vivo models for the development of vaccines and therapeutics. To resolve this, we generated a humanised zebrafish model and determined that neutrophil-specific expression of the human C5a receptor conferred susceptibility to the S. aureus toxins PVL and HlgCB, leading to reduced neutrophil numbers at the site of infection and increased infection-associated mortality. These results show that humanised zebrafish provide a valuable platform to study the contribution of human-specific S. aureus virulence factors to infection in vivo that could facilitate the development of novel therapeutic approaches and essential vaccines.

Original languageEnglish (US)
JournalJournal of Cell Science
Volume134
Issue number5
DOIs
StatePublished - Mar 4 2021

Keywords

  • Host-pathogen interactions
  • Immunology
  • In vivo models
  • Microbiology
  • Staphylococcus aureus
  • Zebrafish

ASJC Scopus subject areas

  • Cell Biology

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