Bacteria-released outer membrane vesicles promote disseminated intravascular coagulation

Abstract

Introduction: Sepsis is frequently complicated by disseminated intravascular coagulation (DIC), which promotes multiple organ dysfunctions and significantly increase the mortality of patients with sepsis. How bacteria cause DIC is not fully understood. Outer membrane vesicles (OMVs) are membrane-enclosed microvesicles released by variety of bacteria. The aim of this study is to determine whether OMVs contribute to the pathogenesis of DIC during bacterial infection.

Methods: Wild-type (WT) or Toll-like receptor 4 (TLR4) knock-out mice were intraperitoneally injected with purified Escherichia coli (E.coli) derived OMVs, or with either wild type E.coli or E.coli with genetic deletion of ypjA, which is critical for OMV's production. Blood samples, liver and lung tissues were collected. The development of DIC was assessed in terms of the occurrence of coagulopathy, the thrombi deposition in livers and lungs, the multiple organ injuries, and the lethality.

Results: Genetic deletion of ypjA significantly attenuated E.coli-induced coagulopathy, intravascular thrombi deposition, multiple organ injuries and mortality, whereas injection of purified E.coli-derived OMVs resulted in the development of DIC in a TLR4-dependent manner.

Conclusions: OMVs importantly contribute to the pathogenesis of DIC during Gram-negative bacterial infection. These findings might open a new avenue to prevent infection-associated coagulopathy by targeting OMVs production.

Keywords: Disseminated intravascular coagulation; Extracellular vesicles; Outer membrane vesicles; Sepsis.