School of Earth Sciences, The Ohio State University, Columbus, OH, 43210, USA; School of Environment and Natural Resources, The Ohio State University, Columbus, OH, 43210, USA.
Departments of Microbiology and Microbial Infection and Immunity, The Ohio State University, 43210, Columbus, OH, USA.
Micron. 2021 Nov;150:103137. doi: 10.1016/j.micron.2021.103137. Epub 2021 Aug 5.
Fibronectin (Fn) and fibrinogen (Fg) are major host proteins present in the extracellular matrix, blood, and coatings on indwelling medical devices. The ability of Staphylococcus aureus to cause infections in humans depends on favorable interactions with these host ligands. Closely related bacterial adhesins, fibronectin-binding proteins A and B (FnBPA, FnBPB) were evaluated for two key steps in pathogenesis: clumping and adhesion. Experiments utilized optical spectrophotometry, flow cytometry, and atomic force microscopy to probe FnBPA/B alone or in combination in seven different strains of S. aureus and Lactococcus lactis, a Gram-positive surrogate that naturally lacks adhesins to mammalian ligands. In the absence of soluble ligands, both FnBPA and FnBPB were capable of interacting with adjacent FnBPs from neighboring bacteria to mediate clumping. In the presence of soluble host ligands, clumping was enhanced particularly under shear stress and with Fn present in the media. FnBPB exhibited greater ability to clump compared to FnBPA. The strength of adhesion was similar for immobilized Fn to FnBPA and FnBPB. These findings suggest that these two distinct but closely related bacterial adhesins, have different functional capabilities to interact with host ligands in different settings (e.g., soluble vs. immobilized). Survival and persistence of S. aureus in a human host may depend on complementary roles of FnBPA and FnBPB as they interact with different conformations of Fn or Fg (compact in solution vs. extended on a surface) present in different physiological spaces.
纤连蛋白（Fn）和纤维蛋白原（Fg）是细胞外基质、血液和留置医疗器械涂层中存在的主要宿主蛋白。金黄色葡萄球菌在人体中引起感染的能力取决于与这些宿主配体的有利相互作用。两种密切相关的细菌黏附素，纤连蛋白结合蛋白 A 和 B（FnBPA、FnBPB）被评估用于发病机制的两个关键步骤：聚集和黏附。实验利用光学分光光度法、流式细胞术和原子力显微镜研究了单独或组合使用的 FnBPA/B 在七种不同的金黄色葡萄球菌和乳球菌中的作用，乳球菌是一种天然缺乏与哺乳动物配体结合的黏附素的革兰氏阳性菌。在没有可溶性配体的情况下，FnBPA 和 FnBPB 都能够与相邻细菌中的相邻 FnBPs 相互作用，介导聚集。在存在可溶性宿主配体的情况下，聚集作用特别是在剪切力存在下并在介质中存在 Fn 时得到增强。FnBPB 比 FnBPA 更能促进聚集。固定化 Fn 与 FnBPA 和 FnBPB 的黏附强度相似。这些发现表明，这两种不同但密切相关的细菌黏附素在不同环境中（例如，可溶性与固定化）与宿主配体相互作用时具有不同的功能能力。金黄色葡萄球菌在人体中的存活和持续存在可能取决于 FnBPA 和 FnBPB 的互补作用，因为它们与不同生理空间中存在的不同构象的 Fn 或 Fg（溶液中紧凑，表面上伸展）相互作用。
