Tryptic Shaving of Staphylococcus aureusUnveils Immunodominant Epitopes on the Bacterial Cell Surface

Autor: Dreisbach, Annette, Wang, Min, van der Kooi-Pol, Magdalena M., Reilman, Ewoud, Koedijk, Dennis G. A. M., Mars, Ruben A. T., Duipmans, José, Jonkman, Marcel, Benschop, Joris J., Bonarius, Hendrik P. J., Groen, Herman, Hecker, Michael, Otto, Andreas, Bäsell, Katrin, Bernhardt, Jörg, Back, Jaap Willem, Becher, Dörte, Buist, Girbe, van Dijl, Jan Maarten
Zdroj: Journal of Proteome Research; August 2020, Vol. 19 Issue: 8 p2997-3010, 14p
Abstrakt: The opportunistic pathogen Staphylococcus aureushas become a major threat for human health and well-being by developing resistance to antibiotics and by fast evolution into new lineages that rapidly spread within the healthy human population. This calls for development of active or passive immunization strategies to prevent or treat acute phase infections. Since no such anti-staphylococcal immunization approaches are available for clinical implementation, the present studies were aimed at identifying new leads for their development. For this purpose, we profiled the cell-surface-exposed staphylococcal proteome under infection-mimicking conditions by combining two approaches for “bacterial shaving” with immobilized or soluble trypsin and subsequent mass spectrometry analysis of liberated peptides. In parallel, non-covalently cell-wall-bound proteins extracted with potassium thiocyanate and the exoproteome fraction were analyzed by gel-free proteomics. All data are available through ProteomeXchange accession PXD000156. To pinpoint immunodominant bacterial-surface-exposed epitopes, we screened selected cell-wall-attached proteins of S. aureusfor binding of immunoglobulin G from patients who have been challenged by different types of S. aureusdue to chronic wound colonization. The combined results of these analyses highlight particular cell-surface-exposed S. aureusproteins with highly immunogenic exposed epitopes as potential targets for development of protective anti-staphylococcal immunization strategies.
Databáze: Supplemental Index