Handling Editor: Derek Walsh
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.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: S.J.F., J.A.G.v.S., S.A.R.; Methodology: K.D.B., M.v.G., T.K.P., N.V.O., S.A.R.; Software: M.v.G.; Validation: K.D.B., M.v.G., T.K.P., S.A.R.; Formal analysis: K.D.B., M.v.G., T.K.P., S.A.R.; Investigation: K.D.B., M.v.G., T.K.P., S.A.R.; Resources: N.V.O., S.J.F., J.A.G.v.S., S.A.R.; Data curation: K.D.B., M.v.G., T.K.P.; Writing - original draft: K.D.B., M.v.G., S.A.R.; Writing - review & editing: K.D.B., M.v.G., S.A.R.; Visualization: K.D.B., M.v.G., S.J.F., J.A.G.v.S., S.A.R.; Supervision: M.v.G., N.V.O., N.W.d.J., J.K., S.J.F., J.A.G.v.S., S.A.R.; Project administration: S.J.F., J.A.G.v.S., S.A.R.; Funding acquisition: S.J.F., J.A.G.v.S., S.A.R.
Funding
This work was supported by AMR cross-council funding from the Medical Research Council to the SHIELD consortium ‘Optimising Innate Host Defence to Combat Antimicrobial Resistance’ (MRNO2995X/1), a Medical Research Council (MRC), United Kingdom, programme grant (MR/M004864/1) to S.A.R., and the University of Sheffield 2022 Futures programme via the Florey Institute. T.K.P. was supported by an individual H2020 Marie Skłodowska-Curie Actions fellowship (PIEF-GA-2013-625975).
Data availability
The raw data for this article is available at Mendeley Data; doi:10.17632/x55r5h6j4g.2.
Supplementary information
Supplementary information available online at https://jcs.biologists.org/lookup/doi/10.1242/jcs.252205.supplemental
- Received August 6, 2020.
- Accepted January 12, 2021.
- © 2021. Published by The Company of Biologists Ltd
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