Staphylococcus aureus colonizes the skin of the majority of patients with atopic dermatitis (AD), and its presence increases disease severity. Adhesion of S. aureus to corneocytes in the stratum corneum is a key initial event in colonization, but the bacterial and host factors contributing to this process have not been defined. Here, we show that S. aureus interacts with the host protein corneodesmosin. Corneodesmosin is aberrantly displayed on the tips of villus-like projections that occur on the surface of AD corneocytes as a result of low levels of skin humectants known as natural moisturizing factor (NMF). An S. aureus mutant deficient in fibronectin binding protein B (FnBPB) and clumping factor B (ClfB) did not bind to corneodesmosin in vitro. Using surface plasmon resonance, we found that FnBPB and ClfB proteins bound with similar affinities. The S. aureus binding site was localized to the N-terminal glycine-serine-rich region of corneodesmosin. Atomic force microscopy showed that the N-terminal region was present on corneocytes containing low levels of NMF and that blocking it with an antibody inhibited binding of individual S. aureus cells to corneocytes. Finally, we found that S. aureus mutants deficient in FnBPB or ClfB have a reduced ability to adhere to low-NMF corneocytes from patients. In summary, we show that FnBPB and ClfB interact with the accessible N-terminal region of corneodesmosin on AD corneocytes, allowing S. aureus to take advantage of the aberrant display of corneodesmosin that accompanies low NMF in AD. This interaction facilitates the characteristic strong binding of S. aureus to AD corneocytes.
|Number of pages
|Proceedings of the National Academy of Sciences of the United States of America
|Early online date
|23 Dec 2020
|Published - 5 Jan 2021
Bibliographical noteFunding Information:
ACKNOWLEDGMENTS. This study was funded by a British Skin Foundation Research Project grant (to J.A.G.). We acknowledge the support of the National Children’s Research Centre, Dublin for our clinical studies. T.M.D.C. is supported by an Irish Research Council Postdoctoral Fellowship. Work at Université Catholique de Louvain was supported by the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme Grant 693630, the National Fund for Scientific Research (FNRS), and FNRS–Walloon Excellence in Life Sciences and Biotechnology (WELBIO) Grants WELBIO-CR-2015A-05 and WELBIO-CR-2019S-01. Y.F.D is a research director at the FNRS. We thank Marta Zapotoczna for assistance with plasmid construction, Tim Foster for helpful discussion, Deirdre Muldowney for technical assistance, and Martin Sutton and Mary Turley for assistance with immunoblotting.
- Staphylococcus aureus
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