A new murine gram-negative sepsis model with standard care satisfies Sepsis-3 and reproduces clinical pathology

Our new abdominal gram-negative murine sepsis model recapitulates key disease outcomes observed in sepsis patients and allows the study of dysfunctional homeostasis in surviving animals. This model can be utilized to identify and test new therapeutics for abdominal gram-negative sepsis or investigate novel mechanisms of immune dysfunction in sepsis survivors. Modifications to our murine model by utilizing alternate clinical pathogens, routes of infection, and mixed-sex, outbred or aged mice are necessary to recapitulate clinical sepsis heterogeneity and address the inherent limitations of preclinical models. Here, our methodology to establish a model with clinical isolates, satisfaction of Sepsis-3 definitions and preclinical sepsis guidelines provides a framework for the development of future models.