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bioRxiv · 10.1101/2025.10.04.680436

The Staphylococcus aureus LXG-domain toxins EsxX and SAR0287 do not promote virulence in a zebrafish larval infection model

Ulhuq, F. R.·Tooke, A.·Mendonca, C.·Casabona, G.·Habersetzer, J.·YANG, Y.·Gomes, M.·Alcock, F.·Mostowy, S.·Palmer, T.
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Abstract

The Staphylococcus aureus type VIIb secretion system (T7SSb) is a multiprotein secretion system that secretes toxins with antibacterial activity, but which is also required for full virulence in animal models of infection. S. aureus strains carry one of four T7SSb locus types, named essC1 to essC4, each of which encodes a characteristic LXG-family substrate at the T7SS locus. In essC2 strains this LXG-domain protein is EsxX, which has a glycine zipper sequence in its C-terminus and has potent antibacterial membrane-depolarising activity. In this work we recognise conserved features of the essC2 and essC3 systems, identifying the LXG protein SAR0287 as structurally and functionally similar to EsxX. Using a zebrafish larval hindbrain ventricle infection model we demonstrate that the T7SSb of essC2 and essC3 representative strains contribute to bacterial replication and zebrafish mortality. However, there is no significant loss of virulence in the model system if EsxX or SAR0287 are absent. These findings indicate there is no discernible role for either toxin in this virulence model.

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Ulhuq, F. R., Tooke, A., Mendonca, C., Casabona, G., Habersetzer, J., YANG, Y., Gomes, M., Alcock, F., Mostowy, S., Palmer, T.. 2025-10-04. The Staphylococcus aureus LXG-domain toxins EsxX and SAR0287 do not promote virulence in a zebrafish larval infection model. https://doi.org/10.1101/2025.10.04.680436

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