Inhibition of O-GlcNAcylation protects from Shiga toxin-mediated cell injury and lethality in host. Academic Article uri icon


  • Shiga toxins (Stxs) produced by enterohemorrhagic 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. Treatment with an O-GlcNAcylation inhibitor remarkably improved the major disease symptoms and survival rate for mice intraperitoneally injected with a lethal dose of Stx. In conclusion, this study elucidates O-GlcNAcylation-dependent pathogenic mechanisms of Stxs and demonstrates that inhibition of aberrant O-GlcNAcylation is a potential approach to treat Stx-mediated diseases.

published proceedings

  • EMBO Mol Med

altmetric score

  • 1.75

author list (cited authors)

  • Lee, K., Lee, J., Lee, P., Jeon, B. C., Song, M. Y., Kwak, S., ... Park, S.

citation count

  • 2

complete list of authors

  • Lee, Kyung-Soo||Lee, Jieun||Lee, Pureum||Jeon, Bong Chan||Song, Min Yeong||Kwak, Sojung||Lee, Jungwoon||Kim, Jun-Seob||Kim, Doo-Jin||Kim, Ji Hyung||Tesh, Vernon L||Lee, Moo-Seung||Park, Sung-Kyun

publication date

  • January 2022