EVALUATION OF ERYPTOSIS INDUCED BY BACTERIAL CONCENTRATIONS IN SEPSIS: A TRANSLATIONAL APPROACH

Sepsis is a life-threatening condition driven by a dysregulated immune response to infection, often leading to multi-organ failure and high mortality. Beyond oxygen transport, red blood cells (RBCs) may contribute to sepsis pathophysiology through eryptosis, a form of programmed RBC death. Characterized by cell shrinkage, membrane changes, and phosphatidylserine exposure, eryptosis can impair microcirculation and tissue oxygenation. This study explored the association between bacterial exposure, eryptosis, and inflammation, assessing its potential as a biomarker for sepsis progression.

Three in vitro experiments were conducted with RBCs from healthy donors. In Experiment I, eryptosis increased over time under control conditions, though activation remained low at 72 hours. Experiment II showed a positive correlation between eryptosis and bacterial concentration, with Staphylococcus aureus (Gram-positive) inducing more eryptosis than Escherichia coli (Gram-negative) at the tested doses. However, Experiment III, which compared bacteria at equal concentrations, found that E. coli induced higher eryptosis levels. These findings suggest S. aureus has a dose-dependent effect, while E. coli may exert a stronger pro-eryptotic influence at similar loads.

Eryptosis may serve as a biomarker of sepsis severity, sensitive to bacterial type and concentration. Gram-negative bacteria, particularly E. coli, caused greater RBC injury, possibly contributing to worse clinical outcomes. These results warrant further investigation into eryptosis as a diagnostic tool and therapeutic target. Enhancing our understanding of eryptosis could support earlier intervention and personalized treatment strategies in sepsis care.