# Enterococcus faecalis Translocation in Sepsis: Fibrinolysis and Mitochondrial Dysfunction Drive Lung Injury

## TL;DR

This study shows how Enterococcus faecalis worsens lung injury in sepsis by disrupting the fibrinolytic system and mitochondrial function, and suggests new treatment approaches.

## Contribution

The study reveals a novel mechanism by which E. faecalis contributes to sepsis-induced lung injury through fibrinolysis and mitochondrial dysfunction.

## Key findings

- E. faecalis exploits fibrinolysis to translocate to the lungs and cause mitochondrial damage.
- Inhibiting fibrinolysis or protecting mitochondria reduces lung injury and inflammation in sepsis.
- Combination therapy with a fibrinolysis inhibitor and mitochondrial protector provides the best protection against lung damage.

## Abstract

Sepsis frequently progresses to acute lung injury (ALI), characterised by inflammation, extracellular matrix degradation, and mitochondrial dysfunction. This study identifies
Enterococcus faecalis
as a gut‐derived bacterium that exploits the host fibrinolytic system for pulmonary translocation, resulting in mitochondrial damage and exacerbating lung injury. Utilising the cecal ligation and puncture (CLP) mouse model combined with
E. faecalis
pulmonary infection, we demonstrated that
E. faecalis
exacerbates lung injury by activating fibrinolysis, disrupting intestinal barrier integrity, and impairing mitochondrial function. Key findings include elevated plasmin activity, increased fibrin degradation products (FDP), and reduced expression of tight junction proteins ZO‐1 and occludin. Mitochondrial dysfunction was confirmed by disrupted ultrastructure, impaired ATP synthesis, and increased ROS levels. Histological analyses revealed severe alveolar damage, neutrophil infiltration, and edema. Treatment with the fibrinolysis inhibitor aminocaproic acid or the mitochondrial protector MitoTEMPO alleviated fibrinolytic activity, preserved mitochondrial function, and reduced lung damage. Notably, combination therapy showed the most significant protective effects, improving lung histology and decreasing inflammation markers. This study provides novel insights into sepsis‐induced lung injury, highlighting
E. faecalis
and the fibrinolytic system as potential therapeutic targets.