The ability of Staphylococcus aureus to colonize the human nares is a crucial pre-requisite for disease. IsdA is a major S. aureus surface protein, expressed during human infection that is required for nasal colonization and survival on human skin. In this work we show that IsdA binds to involucrin, loricrin and cytokeratin K10, proteins present in the cornified envelope of human desquamated epithelial cells. To measure the forces and dynamics of the interaction between IsdA and loricrin (the most abundant protein of the cornified envelope), single-molecule force spectroscopy was used, demonstrating high specificity binding. IsdA acts as a cellular adhesin to the human ligands promoting whole cell binding to immobilized proteins, even in the absence of other S. aureus components (as shown by heterologous expression in Lactococcus lactis). Inhibition experiments revealed binding of the human ligands to the same IsdA region. This region was mapped to the NEAT domain of IsdA. The NEAT domain was also found to be required for S. aureus whole cell binding to the ligands as well as human nasal cells. Thus IsdA is an important adhesin to human ligands predominating in its primary ecological niche.
Clarke, S. R., André, G., Walsh, E. J., Dufrêne, Y., Foster, T. J., & Foster, S. J. (2009). Iron-regulated surface determinant protein A (isdA) mediates adhesion of Staphylococcus aureus to human corneocyte envelope proteins. Infection and Immunity, 77(6), 2408-2416. https://doi.org/10.1128/IAI.01304-08 (Original work published 2009)