Enterohemorrhagic

Background: Outer membrane vesicles (OMVs) secreted by enterohemorrhagic Methods: The sera and kidneys of BALB/c mice orally administered EHEC O157 OMVs were examined for OMVs by immunoelectron and confocal immunofluorescence microscopy. Histopathological evaluation of the kidneys was performed by light and electron microscopy, and blood analyses were conducted using standard methods. The cytotoxicity of EHEC O157 OMVs toward human renal glomerular endothelial cells (HRGECs) and tubular epithelial cells (HK-2) was determined by Cell Death ELISA. In addition, sera from patients with EHEC O157-associated HUS were examined for O157 OMVs by immunoelectron microscopy. Results: EHEC O157 OMVs were detected in the sera and kidneys of mice orally administered 100-400 µg of OMVs. The mice exhibited renal tubular epithelial damage and had significantly increased serum creatinine and blood urea nitrogen levels, indicating acute kidney failure. EHEC O157 OMVs induced apoptosis in HRGECs and HK-2 cells, the primary targets in EHEC-HUS. Moreover, EHEC O157 OMVs were found in the sera of patients with EHEC O157-associated HUS. Conclusion: Orally administered EHEC O157 OMVs translocated from the gastrointestinal tract to the kidneys, where they caused tubular epithelial injury followed by acute kidney failure. Combined with their cytotoxicity toward HRGECs and HK-2 cells and detection in patient sera, these findings indicate that EHEC O157 OMVs contribute to the pathogenesis of EHEC-HUS.