CD9 co-operation with syndecan-1 is required for a major staphylococcal adhesion pathway

Green, L. R.; Issa, R.; Albaldi, F.; Urwin, L.; Khalid, H.; Turner, C. E.; Ciani, B.; Partridge, L. J.; Monk, P. N.

doi:10.1101/2023.01.17.524294

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bioRxiv · 10.1101/2023.01.17.524294

CD9 co-operation with syndecan-1 is required for a major staphylococcal adhesion pathway

Green, L. R.·Issa, R.·Albaldi, F.·Urwin, L.·Khalid, H.·Turner, C. E.·Ciani, B.·Partridge, L. J.·Monk, P. N.

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Abstract

ObjectivesEpithelial colonisation is a critical first step in bacterial pathogenesis. Staphylococcus aureus can utilise several host factors to associate with cells, including 5{beta}l integrin and heparan sulphate proteoglycans, such as the syndecans. Here, we demonstrate that a partner protein of both integrins and syndecans, the host membrane adapter protein tetraspanin CD9, is essential for syndecan-mediated staphylococcal adhesion. Fibronectin is also essential in this process while integrins are only critical for post-adhesion entry into human epithelial cells. Methods and ResultsTreatment of epithelial cells with CD9-derived peptide or heparin caused significant reductions in staphylococcal adherence, dependent on both CD9 and syndecan-1. Exogenous fibronectin caused a CD9-dependent increase in staphylococcal adhesion whereas blockade of {beta}1 integrins did not affect adhesion but did reduce the subsequent internalisation of adhered bacteria. CD9 disruption or deletion increased {beta}1 integrin-mediated internalisation, suggesting that CD9 coordinates sequential staphylococcal adhesion and internalisation. ConclusionsCD9 controls staphylococcal adhesion through syndecan-1, using a mechanism that likely requires CD9-mediated syndecan organisation to correctly display fibronectin at the host cell surface. We propose that CD9-derived peptides or heparin analogues could be developed as anti-adhesion treatments to inhibit the initial stages of staphylococcal pathogenesis.

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Green, L. R., Issa, R., Albaldi, F., Urwin, L., Khalid, H., Turner, C. E., Ciani, B., Partridge, L. J., Monk, P. N.. 2023-01-18. CD9 co-operation with syndecan-1 is required for a major staphylococcal adhesion pathway. https://doi.org/10.1101/2023.01.17.524294

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