Shiga toxin (Stx) type 2-induced increase in O-linked N-acetyl glucosamine protein modification: a new therapeutic target?

Rebecca A Bova, Angela Melton-Celsa

EMBO molecular medicine 2022 Jan 11

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Shiga toxin (Stx)-producing Escherichia coli (STEC) causes bloody diarrhea, which may progress to the potentially fatal hemolytic uremic syndrome (HUS). Development of HUS after STEC infection is dependent on Stx, and is particularly linked to Stx type 2a, Stx2a (Melton-Celsa, 2014; Scheutz, 2014). In this issue of EMBO Molecular Medicine, Lee et al report that O-linked N-acetyl glucosamine protein modification (O-GlcNAcylation) is increased in host cells after Stx exposure and the subsequent endoplasmic reticulum (ER) stress response. The elevated O-GlcNAcylation resulted in elevated inflammatory and apoptotic processes. Inhibition of O-GlcNAcylation with OSMI-1 protected cells from the Stx2a-induced damage. In mice intoxicated with Stx2a, OSMI-1 treatment reduced kidney damage and increased mouse survival. © 2021 The Authors. Published under the terms of the CC BY 4.0 license.

Citation

Rebecca A Bova, Angela Melton-Celsa. Shiga toxin (Stx) type 2-induced increase in O-linked N-acetyl glucosamine protein modification: a new therapeutic target? EMBO molecular medicine. 2022 Jan 11;14(1):e15389