دورية أكاديمية
Staphylococcus aureus adhesion in endovascular infections is controlled by the ArlRS-MgrA signaling cascade.
| العنوان: | Staphylococcus aureus adhesion in endovascular infections is controlled by the ArlRS-MgrA signaling cascade. |
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| المؤلفون: | Jakub M Kwiecinski, Heidi A Crosby, Claire Valotteau, Joseph A Hippensteel, Manasa K Nayak, Anil K Chauhan, Eric P Schmidt, Yves F Dufrêne, Alexander R Horswill |
| المصدر: | PLoS Pathogens, Vol 15, Iss 5, p e1007800 (2019) |
| بيانات النشر: | Public Library of Science (PLoS), 2019. |
| سنة النشر: | 2019 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Biology (General) |
| مصطلحات موضوعية: | Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5 |
| الوصف: | Staphylococcus aureus is a leading cause of endovascular infections. This bacterial pathogen uses a diverse array of surface adhesins to clump in blood and adhere to vessel walls, leading to endothelial damage, development of intravascular vegetations and secondary infectious foci, and overall disease progression. In this work, we describe a novel strategy used by S. aureus to control adhesion and clumping through activity of the ArlRS two-component regulatory system, and its downstream effector MgrA. Utilizing a combination of in vitro cellular assays, and single-cell atomic force microscopy, we demonstrated that inactivation of this ArlRS-MgrA cascade inhibits S. aureus adhesion to a vast array of relevant host molecules (fibrinogen, fibronectin, von Willebrand factor, collagen), its clumping with fibrinogen, and its attachment to human endothelial cells and vascular structures. This impact on S. aureus adhesion was apparent in low shear environments, and in physiological levels of shear stress, as well as in vivo in mouse models. These effects were likely mediated by the de-repression of giant surface proteins Ebh, SraP, and SasG, caused by inactivation of the ArlRS-MgrA cascade. In our in vitro assays, these giant proteins collectively shielded the function of other surface adhesins and impaired their binding to cognate ligands. Finally, we demonstrated that the ArlRS-MgrA regulatory cascade is a druggable target through the identification of a small-molecule inhibitor of ArlRS signaling. Our findings suggest a novel approach for the pharmacological treatment and prevention of S. aureus endovascular infections through targeting the ArlRS-MgrA regulatory system. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1553-7366 1553-7374 |
| Relation: | https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374 |
| DOI: | 10.1371/journal.ppat.1007800 |
| URL الوصول: | https://doaj.org/article/a054eb9fbd2c4c719f03495349f5698f |
| رقم الأكسشن: | edsdoj.054eb9fbd2c4c719f03495349f5698f |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15537366 15537374 |
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| DOI: | 10.1371/journal.ppat.1007800 |