Force Nanoscopy Demonstrates Stress-Activated Adhesion between Iron-Regulated Surface Determinant Protein B and Host Toll-like Receptor 4.

The 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 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.

The endothelium at the interface between tissues and in the bloodstream.

SUMMARY is a major human pathogen. It can cause many types of infections, in particular bacteremia, which frequently leads to infective endocarditis, osteomyelitis, sepsis, and other debilitating diseases. The development of secondary infections is based on the bacterium's ability to associate with endothelial cells lining blood vessels.

Nanomechanics of CCN1-Mediated Phagocytosis.

Phagocytosis is an essential mechanism of the human immune system where pathogens are eliminated by immune cells. The CCN1 protein plays an important role in the phagocytosis of by favoring the bridging of the αβ integrin to the bacterial peptidoglycan (PG), through mechanical forces that remain unknown. Here, we employ single-molecule experiments to unravel the nanomechanics of the PG-CCN1-αβ ternary complex.

Searching for Virulence Factors among Isolates from Orthopedic Infections: Correlation of , and Genes with Hemolytic Activity and Synergistic Hemolytic Activity.

is an emerging high-virulent pathogen. Here, the presence and expression of virulence genes (, , , , , and , and genes of the putative and ) and the ability to induce synergistic hemolytic activity and hemolysis after 24, 48 and 72 h were investigated in a collection of twenty-two clinical isolates. The collection of isolates, mainly from implant orthopedic infections, had previously been grouped by ribotyping/dendrogram analysis and studied for biofilm matrices, biomasses and antibiotic resistances.

von Willebrand factor-binding protein (vWbp)-activated factor XIII and transglutaminase 2 (TG2) promote cross-linking between FnBPA from Staphylococcus aureus and fibrinogen.

The secreted von Willebrand factor-binding protein (vWbp) from Staphylococcus aureus interacts with the coagulation factors prothrombin and fibrinogen (Fbg), leading to the non-proteolytic transglutaminase activation of Factor XIII (FXIII). In this study we found that vWbp-activated FXIII catalyses the incorporation of amino-donor dansylcadaverine into region A of fibronectin-binding protein A (FnBPA). Incubation of Fbg with recombinant region A of S.