The bacterial pathogen Staphylococcus pseudintermedius is involved in canine otitis externa and pyoderma as well as in surgical wound and urinary tract infections. Invasion of canine epithelial cells is promoted by S. pseudintermedius fibronectin (Fn)-binding proteins SpsD and SpsL through molecular interactions that are currently unknown. By means of single-molecule experiments, we discover that both adhesins have distinct molecular mechanisms for binding to Fn. We show that the SpsD-Fn interaction has a strength equivalent to that of a covalent bond (∼1.5 to 1.8 nN), which is an order of magnitude stronger than the binding force of classical receptor-ligand complexes. We suggest that this extreme mechanostability originates from the β-sheet organization of a tandem β-zipper. Upon binding to FnI modules, the intrinsically disordered binding sequences of SpsD would shift into an ordered structure by forming additional β-strands along triple peptide β-sheets in the Fn molecule. Dynamic force measurements reveal an unexpected behavior, i.e., that strong bonds are activated by mechanical tension as observed with catch bonds. By contrast, the SpsL-Fn interaction involves multiple weak bonds (∼0.2 nN) that rupture sequentially under force. Together with the recently described dock, lock, and latch complex, the ultrastrong interaction unraveled here is among the strongest noncovalent biological interaction measured to date. Our findings may find applications for the identification of inhibitory compounds to treat infections triggered by pathogens engaged in tandem β-zipper interactions.

中文翻译：

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葡萄球菌黏附素SpsD和纤连蛋白之间的分子复合物维持纳米牛顿范围内的机械力。

细菌病原体伪葡萄球菌与犬外耳炎和脓皮病以及外科伤口和尿路感染有关。伪中间链球菌促进犬上皮细胞的侵袭纤连蛋白（Fn）结合蛋白SpsD和SpsL通过目前未知的分子相互作用。通过单分子实验，我们发现这两种粘附素都具有与Fn结合的独特分子机制。我们表明，SpsD-Fn相互作用的强度等于共价键的强度（约1.5至1.8 nN），比经典受体-配体复合物的结合力强一个数量级。我们建议这种极强的机械性能源自串联β-拉链的β-折叠结构。与FnI模块结合后，SpsD固有的无序结合序列将通过沿着Fn分子中的三肽β-折叠形成额外的β-链而转变为有序结构。动态力测量显示出意外的行为，即 如捕获键所观察到的那样，强键被机械张力激活。相比之下，SpsL-Fn相互作用涉及多个弱键（〜0.2 nN），这些弱键在力的作用下依次破裂。与最近描述的坞，锁和闩锁复合体一起，此处揭示的超强相互作用是迄今为止测得的最强的非共价生物相互作用之一。我们的发现可能可用于鉴定抑制性化合物，以治疗由参与串联β-拉链相互作用的病原体引发的感染。此处揭示的超强相互作用是迄今为止测得的最强的非共价生物相互作用之一。我们的发现可能可用于鉴定抑制性化合物，以治疗由参与串联β-拉链相互作用的病原体引发的感染。此处揭示的超强相互作用是迄今为止测得的最强的非共价生物相互作用之一。我们的发现可能可用于鉴定抑制性化合物，以治疗由参与串联β-拉链相互作用的病原体引发的感染。