Enterohemorrhagic Escherichia coli O157 outer membrane vesicles administered by oral gavage cause renal tubular injury and acute kidney failure in mice

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064173%3A_____%2F25%3A43929209" target="_blank" >RIV/00064173:_____/25:43929209 - isvavai.cz</a>

Alternative codes found

RIV/75010330:_____/25:00015121 RIV/00216208:11120/25:43929209 RIV/00216208:11130/25:10506519 RIV/00064203:_____/25:10506519

Result on the web

<a href="https://doi.org/10.3389/fcimb.2025.1704731" target="_blank" >https://doi.org/10.3389/fcimb.2025.1704731</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fcimb.2025.1704731" target="_blank" >10.3389/fcimb.2025.1704731</a>

Result language

angličtina

Original language name

Enterohemorrhagic Escherichia coli O157 outer membrane vesicles administered by oral gavage cause renal tubular injury and acute kidney failure in mice

Original language description

Background Outer membrane vesicles (OMVs) secreted by enterohemorrhagic Escherichia coli (EHEC) O157 contain Shiga toxin 2 (Stx2), the major virulence factor involved in the pathogenesis of EHEC-associated hemolytic uremic syndrome (EHEC-HUS). However, it remains unclear whether EHEC OMVs produced in the human intestine during infection play a role in EHEC-HUS development. Using a mouse model, we investigated whether EHEC O157 OMVs administered by oral gavage translocate from the gastrointestinal tract to the bloodstream, enter the kidneys, and induce signs of EHEC-HUS. Because mice, unlike humans, express the Stx2 receptor Gb3 on the renal tubular epithelium but not on the glomerular endothelium, we focused on the ability of EHEC O157 OMVs to cause tubular damage, which represents a mechanism that, alongside glomerular thrombotic microangiopathy (TMA), contributes to acute kidney failure in EHEC-HUS.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 mu g 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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30303 - Infectious Diseases

Project

<a href="/en/project/GA21-06792S" target="_blank" >GA21-06792S: Involvement of outer membrane vesicles, novel virulence tools of enterohemorrhagic Escherichia coli, in the pathogenesis of hemolytic-uremic syndrome</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Frontiers in Cellular and Infection Microbiology

ISSN

2235-2988

e-ISSN

2235-2988

Volume of the periodical

15

Issue of the periodical within the volume

November

Country of publishing house

CH - SWITZERLAND

Number of pages

20

Pages from-to

1704731

UT code for WoS article

001631962400001

EID of the result in the Scopus database

2-s2.0-105024097491