Rapid Aggregation of Staphylococcus aureus in Synovial Fluid Is Influenced by Synovial Fluid Concentration, Viscosity, and Fluid Dynamics, with Evidence of Polymer Bridging.

Early bacterial survival in the postsurgical joint is still a mystery. Recently, synovial fluid-induced aggregation was proposed as a potential mechanism of bacterial protection upon entry into the joint. As synovial fluid is secreted back into the joint cavity following surgery, rapid fluctuations in synovial fluid concentrations, composition, and viscosity occur. These changes, along with fluid movement resulting from postoperative joint motion, modify the environment and potentially affect the kinetics of aggregate formation. Through this work, we sought to evaluate the influence of exposure time, synovial fluid concentration, viscosity, and fluid dynamics on aggregation. Furthermore, we aimed to elucidate the primary mechanism of aggregate formation by assessing the interaction of bacterial adhesins with the synovial fluid polymer fibrinogen. Following incubation under each simulated postoperative joint condition, the aggregates were imaged using confocal microscopy. Our analysis revealed the formation of two distinct aggregate phenotypes, depending on whether the incubation was conducted under static or dynamic conditions. Using a surface adhesin mutant, we have narrowed down the genetic determinants for synovial fluid aggregate formation and identified essential host polymers. We report here that synovial fluid-induced aggregation is influenced by various changes specific to the postsurgical joint environment. While we now have evidence that select synovial fluid polymers facilitate bridging aggregation through essential bacterial adhesins, we suspect that their utility is limited by the increasing viscosity under static conditions. Furthermore, dynamic fluid movement recovers the ability of the bacteria with surface proteins present to aggregate under high-viscosity conditions, yielding large, globular aggregates.