{"title":"力纳米显微镜显示金黄色葡萄球菌铁调控的表面决定蛋白B和宿主toll样受体4之间的应力激活粘附","authors":"Telmo O. Paiva, Pietro Speziale, Yves F. Dufrêne","doi":"10.1021/acsnano.4c12648","DOIUrl":null,"url":null,"abstract":"The <i>Staphylococcus aureus</i> iron-regulated surface determinant protein B (IsdB) has recently been shown to bind to toll-like receptor 4 (TLR4), thereby inducing a strong inflammatory response in innate immune cells. Currently, two unsolved questions are (i) What is the molecular mechanism of the IsdB-TLR4 interaction? and (ii) Does it also play a role in nonimmune systems? Here, we use single-molecule experiments to demonstrate that IsdB binds TLR4 with both weak and extremely strong forces and that the mechanostability of the molecular complex is dramatically increased by physical stress, sustaining forces up to 2000 pN, at a loading rate of 10<sup>5</sup> pN/s. We also show that TLR4 binding by IsdB mediates time-dependent bacterial adhesion to endothelial cells, pointing to the role of this bond in cell invasion. Our findings point to a function for IsdB in pathogen–host interactions, that is, mediating strong bacterial adhesion to host endothelial cells under fluid shear stress, unknown until now. In nanomedicine, this stress-dependent adhesion represents a potential target for innovative therapeutics against <i>S. aureus</i>-resistant strains.","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"15 1","pages":""},"PeriodicalIF":16.0000,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Force Nanoscopy Demonstrates Stress-Activated Adhesion between Staphylococcus aureus Iron-Regulated Surface Determinant Protein B and Host Toll-like Receptor 4\",\"authors\":\"Telmo O. Paiva, Pietro Speziale, Yves F. Dufrêne\",\"doi\":\"10.1021/acsnano.4c12648\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"The <i>Staphylococcus aureus</i> iron-regulated surface determinant protein B (IsdB) has recently been shown to bind to toll-like receptor 4 (TLR4), thereby inducing a strong inflammatory response in innate immune cells. Currently, two unsolved questions are (i) What is the molecular mechanism of the IsdB-TLR4 interaction? and (ii) Does it also play a role in nonimmune systems? Here, we use single-molecule experiments to demonstrate that IsdB binds TLR4 with both weak and extremely strong forces and that the mechanostability of the molecular complex is dramatically increased by physical stress, sustaining forces up to 2000 pN, at a loading rate of 10<sup>5</sup> pN/s. We also show that TLR4 binding by IsdB mediates time-dependent bacterial adhesion to endothelial cells, pointing to the role of this bond in cell invasion. Our findings point to a function for IsdB in pathogen–host interactions, that is, mediating strong bacterial adhesion to host endothelial cells under fluid shear stress, unknown until now. In nanomedicine, this stress-dependent adhesion represents a potential target for innovative therapeutics against <i>S. aureus</i>-resistant strains.\",\"PeriodicalId\":21,\"journal\":{\"name\":\"ACS Nano\",\"volume\":\"15 1\",\"pages\":\"\"},\"PeriodicalIF\":16.0000,\"publicationDate\":\"2024-12-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Nano\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://doi.org/10.1021/acsnano.4c12648\",\"RegionNum\":1,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Nano","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1021/acsnano.4c12648","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Force Nanoscopy Demonstrates Stress-Activated Adhesion between Staphylococcus aureus Iron-Regulated Surface Determinant Protein B and Host Toll-like Receptor 4
The Staphylococcus aureus iron-regulated surface determinant protein B (IsdB) has recently been shown to bind to toll-like receptor 4 (TLR4), thereby inducing a strong inflammatory response in innate immune cells. Currently, two unsolved questions are (i) What is the molecular mechanism of the IsdB-TLR4 interaction? and (ii) Does it also play a role in nonimmune systems? Here, we use single-molecule experiments to demonstrate that IsdB binds TLR4 with both weak and extremely strong forces and that the mechanostability of the molecular complex is dramatically increased by physical stress, sustaining forces up to 2000 pN, at a loading rate of 105 pN/s. We also show that TLR4 binding by IsdB mediates time-dependent bacterial adhesion to endothelial cells, pointing to the role of this bond in cell invasion. Our findings point to a function for IsdB in pathogen–host interactions, that is, mediating strong bacterial adhesion to host endothelial cells under fluid shear stress, unknown until now. In nanomedicine, this stress-dependent adhesion represents a potential target for innovative therapeutics against S. aureus-resistant strains.
期刊介绍:
ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.