Variable Staphylothrombin Activity in Staphylococcus aureus Bloodstream Infections

Abstract Background Although manipulation of host hemostasis is a central mechanism in Staphylococcus aureus virulence, clinically relevant phenotypes of S aureus coagulase activity and the variability thereof in the context of bloodstream infections are unknown. Methods We created a high-throughput staphylothrombin activity and growth fitness assay to characterize fibrin formation and S aureus replication by adding bacterial culture supernatant to human blood plasma. Supernatant is rich in bacterial proteins, including coagulases secreted during growth, but it contains relatively few viable cells. As a result, staphylothrombin activity driven by secreted coagulases can initially be observed and a contribution from bacterial replication can also be captured. Results Some S aureus isolates showed slow or absent staphylothrombin activity in a subset of plasma specimens despite robust and rapid fibrin polymerization in other plasmas, suggesting that a host-pathogen match or mismatch determines the observed phenotype. Characterization of S aureus transposon mutant behavior, host plasma coagulation factors, pharmacologic direct thrombin inhibition, and across-host patterns provides clues to complex determinants of coagulase-mediated virulence. Conclusions Observations of variable staphylothrombin phenotypes may have implications for novel therapeutic approaches and clinical risk stratification in S aureus bloodstream infections.