Inhibition of O-GlcNAcylation protects from Shiga toxin-mediated cell injury and lethality in host

ABSTRACT: Shiga toxins (Stxs) produced by enterohaemorrhagic Escherichia coli (EHEC) are the major virulence factors responsible for hemorrhagic colitis, which can lead to life-threatening systemic complications including acute renal failure (hemolytic uremic syndrome) and neuropathy. Here, we report that O-GlcNAcylation, a type of post-translational modification, was acutely increased upon induction of endoplasmic reticulum (ER) stress in host cells by Stxs. Suppression of the abnormal Stx-mediated increase in O-GlcNAcylation effectively inhibited apoptotic and inflammatory responses in Stx-susceptible cells. The protective effect of O-GlcNAc inhibition for Stx-mediated pathogenic responses was also verified using three dimensional (3D)-cultured spheroids or organoids mimicking the human kidney. Tr

SUBMITTER: Dr. SUNG-KYUN PARK 

PROVIDER: S-SCDT-EMM-2021-14678 | biostudies-other |

REPOSITORIES: biostudies-other