Immune recognition of Staphylococcus aureus wall teichoic acid

Publication date

2019-04-11

Authors

van Dalen, Rob

Editors

Advisors

Supervisors

van Strijp, JosORCID 0000-0001-6253-0830ISNI 0000000395049175
van Sorge, NinaISNI 000000039584948X

DOI

Document Type

Dissertation

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Abstract

The bacterium Staphylococcus aureus can often be found on our skin and in our nose, but also frequently causes severe infections. Especially infections with antibiotic-resistant S. aureus (MRSA) are difficult to treat. We investigated the recognition of a unique structure of the S. aureus cell wall by the human immune system. New insights into these interactions may be used in the development of new treatment strategies against S. aureus. We specifically focused on a sugarcoated structure of the S. aureus cell wall, known as wall teichoic acid (WTA). We describe how S. aureus WTA is recognized by langerin, a receptor on skin immune cells and subsequently induces skin inflammation. Importantly, langerin discriminates S. aureus from other staphylococcal species. This may provide a possible explanation for the association between S. aureus, but not other staphylococcal species, and the allergic skin disorder eczema. In addition, we developed a new method to analyze antibodies targeting WTA variants, which differ between group of S. aureus bacteria. To do so, we produced the WTA variants in the lab, and used these to analyze their recognition by antibodies present in human blood. Using this method, we measured the recognition by antibodies on pure WTA, which greatly improved the sensitivity of the analytic assay. Beyond the use of these WTA compounds in analytical methods, they can potentially be used in an S. aureus vaccine. Our work shows that WTA is a promising target for new treatment strategies against S. aureus.

Keywords

Staphylococcus aureus, glycobiology, wall teichoic acid, langerin, langerhans cell, antibodies, vaccine

Citation

van Dalen, R 2019, 'Immune recognition of Staphylococcus aureus wall teichoic acid', UMC Utrecht, [Utrecht].