The Temperature Dependence of the Pathogenic Bacterial Adhesin Complex SdrG:Fgβ under Sustained Loads: A High-Force Slip Bond

Staphylococcus epidermidis is the leading cause of medical-implant-related infections. This pathogen attaches to medical implants coated in host fibrinogen via adhesin proteins. To resist high shear forces, adhesin-ligand rupture forces can exceed 2000 pN, a force that is much higher than streptavidin–biotin (150–300 pN). Yet, these adhesin-ligand complexes have a quite moderate KD (∼380 nM). This nanomechanics is explained, in part, by catch-bond behavior where adhesin-ligand lifetimes increase with force. Notably, prior reports of adhesin catch-bond mechanics at both low (3–30 pN) and high (1100–1400 pN) forces have lifetimes that are difficult to reconcile. Here, we combined constant-velocity and constant-force assays and thereby showed slip-bond behavior over six decades of lifetimes first for SdrG:Fgβ (1000–2400 pN) and then for SdrE:CFH (800–2200 pN) from Staphylococcus aureus. Individual lifetimes for SdrE:CFH exceeded 15 min at 800 pN. To investigate the thermodynamics of SdrG:Fgβ stability, we measured its lifetime using the constant-force assay as a function of both force (1000–1800 pN) and temperature (10–37 °C). Analysis yielded the enthalpic-dissociation barrier (ΔH‡ = 40 ± 4 kBT) and, assuming an enthalpy-dominated barrier, the dissociation attempt frequency (∼6 × 1010 s–1). Our results unambiguously demonstrate high-force slip-bond behavior for two different adhesin-ligand pairs and provide biophysical parameters governing the stability of key virulence factors.