Outer membrane vesicles derived from Escherichia coli induce systemic inflammatory response syndrome.
Sepsis, characterized by a systemic inflammatory state that is usually related to Gram-negative bacterial infection, is a leading cause of death worldwide. Although the annual incidence of sepsis is still rising, the exact cause of Gram-negative bacteria-associated sepsis is not clear. Outer membrane vesicles (OMVs), constitutively secreted from Gram-negative bacteria, are nano-sized spherical bilayered proteolipids. Using a mouse model, we showed that intraperitoneal injection of OMVs derived from intestinal Escherichia coli induced lethality. Furthermore, OMVs induced host responses which resemble a clinically relevant condition like sepsis that was characterized by piloerection, eye exudates, hypothermia, tachypnea, leukopenia, disseminated intravascular coagulation, dysfunction of the lungs, hypotension, and systemic induction of tumor necrosis factor-alpha and interleukin-6. Our study revealed a previously unidentified causative microbial signal in the pathogenesis of sepsis, suggesting OMVs as a new therapeutic target to prevent and/or treat severe sepsis caused by Gram-negative bacterial infection.
Park
Kyong-Su
KS
Division of Molecular and Life Sciences, Department of Life Science, Pohang University of Science and Technology, Pohang, Republic of Korea.
Choi
Kyoung-Ho
KH
Kim
You-Sun
YS
Hong
Bok Sil
BS
Kim
Oh Youn
OY
Kim
Ji Hyun
JH
Yoon
Chang Min
CM
Koh
Gou-Young
GY
Kim
Yoon-Keun
YK
Gho
Yong Song
YS
D000818:Animals; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000502:physiology*; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D011510:Proteolipids / Q000502:physiology*; D018746:Systemic Inflammatory Response Syndrome / Q000382:microbiology*
D011510:Proteolipids