Time-dependent changes to sepsis-specific networks in the plasma proteome are mechanistic readouts of sepsis progression.

Abstract

Sepsis accounts for 1 in 5 deaths globally and is the most common cause of deaths in U.S. hospitals. Despite this public health burden, no diagnostic biomarker, nor therapeutic agent for sepsis has proven useful or effective. The principal obstacle is the lack of a mechanistic understanding of this syndrome, particularly during its onset and progression. Using an experimental model of murine sepsis, we report here a time-dependent assessment of changes to the plasma proteome upon infection with Salmonella enterica serovar Typhimurium. Changes to the plasma proteome signature of sepsis (PPSS) revealed a transition from early inflammation and coagulation to a later stage of chronic inflammation, coagulopathy and bacteremia. This study represents an advance in our understanding of sepsis progression that may guide innovative therapeutic attitudes and help clinicians track sepsis progression.