Staphylococcus aureus Fibronectin-Binding Protein A Mediates Cell-Cell Adhesion through Low-Affinity Homophilic Bonds.
Staphylococcus aureus Fibronectin-Binding Protein A Mediates Cell-Cell Adhesion through Low-Affinity Homophilic Bonds.
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DOI：
10.1128/mbio.00413-15
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发表时间：
2015-05-26
期刊：
影响因子：
6.4
通讯作者：
Dufrêne YF
中科院分区：
文献类型：
--
作者：
Herman-Bausier P;El-Kirat-Chatel S;Foster TJ;Geoghegan JA;Dufrêne YF
金黄色葡萄球菌是一种重要的条件致病菌，是导致留置医疗器械生物被膜相关感染的主要原因。位于细胞表面的纤连蛋白结合蛋白A（FnBPA）在耐甲氧西林金黄色葡萄球菌（MRSA）生物膜形成的积累阶段起重要作用，但潜在的分子相互作用尚未建立。在这里，我们使用单细胞和单分子原子力显微镜来解开FnBPA介导细胞间粘附的机制。我们表明，FnBPA是负责特定的细胞间的相互作用，涉及FnBPA的A域，并导致微尺度细胞聚集。我们证明了FnBPA介导的粘附的强度来源于相邻细胞上FnBPA A结构域之间的多个低亲和力亲同种相互作用。通过FnBPA的低亲和力结合可能对生物膜动力学很重要。这些结果为FnBPA在金黄色葡萄球菌生物膜形成过程中促进细胞积累的能力提供了分子基础。我们推测，嗜同性相互作用可能代表了葡萄球菌细胞表面蛋白指导细胞间粘附的一种通用策略。由于MRSA菌株的生物膜形成依赖于蛋白质而不是多糖，我们的方法为设计药物或疫苗以抑制MRSA生物膜中蛋白质依赖性细胞间相互作用提供了令人兴奋的前景。金黄色葡萄球菌是一种人类病原体，可在留置医疗器械（如中心静脉导管和假体关节）上形成生物膜。这导致难以用抗生素治疗的生物膜感染，因为生物膜基质内的许多细胞是休眠的。纤连蛋白结合蛋白（FnBPs）FnBPA和FnBPB促进临床相关的耐甲氧西林金黄色葡萄球菌（MRSA）菌株的生物膜形成，但所涉及的分子机制仍然知之甚少。我们使用原子力显微镜技术，以证明FnBPA介导的细胞间粘附通过多个，低亲和力的亲同性键之间的FnBPA A结构域对相邻细胞。因此，FnBP介导的嗜同性相互作用代表了预防MRSA生物膜的有趣靶点。我们建议，这种嗜同性机制可能是广泛的葡萄球菌细胞表面蛋白，提供了一种手段，以指导细胞间粘附和生物膜积累。
Staphylococcus aureus is an important opportunistic pathogen which is a leading cause of biofilm-associated infections on indwelling medical devices. The cell surface-located fibronectin-binding protein A (FnBPA) plays an important role in the accumulation phase of biofilm formation by methicillin-resistant S. aureus (MRSA), but the underlying molecular interactions are not yet established. Here, we use single-cell and single-molecule atomic force microscopy to unravel the mechanism by which FnBPA mediates intercellular adhesion. We show that FnBPA is responsible for specific cell-cell interactions that involve the FnBPA A domain and cause microscale cell aggregation. We demonstrate that the strength of FnBPA-mediated adhesion originates from multiple low-affinity homophilic interactions between FnBPA A domains on neighboring cells. Low-affinity binding by means of FnBPA may be important for biofilm dynamics. These results provide a molecular basis for the ability of FnBPA to promote cell accumulation during S. aureus biofilm formation. We speculate that homophilic interactions may represent a generic strategy among staphylococcal cell surface proteins for guiding intercellular adhesion. As biofilm formation by MRSA strains depends on proteins rather than polysaccharides, our approach offers exciting prospects for the design of drugs or vaccines to inhibit protein-dependent intercellular interactions in MRSA biofilms. Staphylococcus aureus is a human pathogen that forms biofilms on indwelling medical devices, such as central venous catheters and prosthetic joints. This leads to biofilm infections that are difficult to treat with antibiotics because many cells within the biofilm matrix are dormant. The fibronectin-binding proteins (FnBPs) FnBPA and FnBPB promote biofilm formation by clinically relevant methicillin-resistant S. aureus (MRSA) strains, but the molecular mechanisms involved remain poorly understood. We used atomic force microscopy techniques to demonstrate that FnBPA mediates cell-cell adhesion via multiple, low-affinity homophilic bonds between FnBPA A domains on adjacent cells. Therefore, FnBP-mediated homophilic interactions represent an interesting target to prevent MRSA biofilms. We propose that such homophilic mechanisms may be widespread among staphylococcal cell surface proteins, providing a means to guide intercellular adhesion and biofilm accumulation.