Microbial proteases and endothelial barrier disruption in sepsis: A neglected nexus

Area of Science:

• Microbiology
• Immunology
• Vascular Biology

Background:

• Sepsis is a global health crisis driven by dysregulated host responses to infection.
• Host inflammatory pathways are well-studied, but bacterial protease contributions to sepsis are often overlooked.
• Bacterial proteases are emerging as critical virulence factors in sepsis pathogenesis.

Purpose of the Study:

• To review the mechanisms by which bacterial proteases contribute to sepsis.
• To highlight key microbial proteases involved in sepsis.
• To discuss diagnostic challenges and therapeutic strategies targeting bacterial proteases in sepsis.

Main Methods:

• Literature review of mechanistic insights into bacterial proteases in sepsis.
• Summary of experimental models used to study protease activity in sepsis.
• Analysis of diagnostic challenges and emerging therapeutic approaches.

Main Results:

• Bacterial proteases damage the vascular endothelium by cleaving junctional proteins and degrading the glycocalyx.
• These proteases inactivate anticoagulant molecules and degrade coagulation factors, leading to endothelial barrier failure and disseminated intravascular coagulation (DIC).
• Bacterial proteases also exacerbate inflammation by increasing cytokine release and degrading complement components.

Conclusions:

• Bacterial proteases are significant contributors to sepsis pathogenesis through direct damage to the vascular endothelium and promotion of thrombo-inflammation.
• Understanding the roles of specific proteases like EspP, Protease IV, LasB, and SpeB is crucial.
• Targeting bacterial proteases represents a promising therapeutic avenue for improving sepsis outcomes.