Structure, Mechanics, and Instability of Fibrin Clot Infected with Staphylococcus epidermidis

Abstract

Health care-associated infection, over half of which can be attributed to indwelling medical devices, is a strong risk factor for thromboembolism. Although most experimental models of medical device infection draw upon isolated bacterial biofilms, in fact there is no infection without host protein contribution. Here we study, to our knowledge, a new model for medical device infection-that of an infected fibrin clot-and show that the common blood-borne pathogen Staphylococcus epidermidis influences this in vitro model of a blood clot mechanically and structurally on both microscopic and macroscopic scales. Bacteria present during clot formation produce a visibly disorganized microstructure that increases clot stiffness and triggers mechanical instability over time. Our results provide insight into the observed correlation between medical device infection and thromboembolism; the increase in model clot heterogeneity shows that S. epidermidis can rupture a fibrin clot. The resultant embolization of the infected clot can contribute to the systemic dissemination of the pathogen.

Staphylococcus epidermidis Has Growth Phase Dependent Affinity for Fibrinogen and Resulting Fibrin Clot Elasticity

“…Clot formation during rheometry is observed by rapid increase in the linear elastic modulus (G ) over time (Figure 3A). Based on our previous work (Ma et al, 2017) and reproduced here for purposes of comparison, the G of a pure fibrin clot (0.5 mg/mL fibrinogen) without bacterial cells reaches a steady-state at about 40 min with a value of 1.5 ± 0.2 Pa. The addition of stationary phase S. epidermidis retards clot formation with a two-step kinetic profile of G (Figure 3A), consistent with our previous work (Ma et al, 2017).…”

“…The fibrin network structure formed in the presence of exponential phase S. epidermidis remains homogeneous (Figure 3D) and the mesh size is slightly increased (7.0 ± 0.5 µm) over pure fibrin (p = 0.023). In comparison, the network formed in the presence of stationary phase S. epidermidis is heterogeneous (Figure 3E) with two characteristic mesh sizes (2.6 ± 0.8 and 23.1 ± 6.8 µm), as previously reported (Ma et al, 2017), which are significantly different than either pure fibrin or fibrin with exponential phase cells (p < 10 −5 ). We also observed that the exponential phase cells are localized to the voids of the fibrin network (Figure 3D) rather than bound to the fibrin fibers as seen for stationary phase cells (Figure 3E).…”

Networks that stop the flow: A fresh look at fibrin and neutrophil extracellular traps

“…The fibrin network is generally formed of thicker fibers (ranging generally between 100 and 200 nm with pore diameters ranging from 0.1 to 5 μm [133,134]. However, a multitude of factors influence the final structure (concentrations of thrombin, fibrinogen, ionic strength, pH, presence of plasma proteins, histones, DNA, cells, and even bacteria themselves [135], as reviewed in [37,123]. Furthermore, the network is largely heterogeneous (e.g.…”

Damped White Noise Diffusion with Memory for Diffusing Microprobes in Ageing Fibrin Gels

“…Aside from its importance in clinical applications, fibrin also finds an increasing role in tissue regeneration and engineering (5,7,8). Thus, it is important to have a quantitative description of the mechanics and complex structural formation of fibrin as a viscoelastic biomaterial (3,(9)(10)(11). Because not much is known about the diffusive behavior of probe particles in fibrin as its structure evolves in time, we use passive microrheology via videomicroscopy to reveal the gelation dynamics of fibrin by tracking the movement of probe particles suspended in its network of protein polymers (12)(13)(14).…”