Fighting Shigella by Blocking Its Disease-Causing Toxin.

Diksha Haksar, Mostafa Asadpoor, Torben Heise, Jie Shi, Saskia Braber, Gert Folkerts, Lluis Ballell, Janneth Rodrigues, Roland J Pieters

Journal of medicinal chemistry 2021 May 13

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Shiga toxin is an AB5 toxin produced by Shigella species, while related toxins are produced by Shiga toxin-producing Escherichia coli (STEC). Infection by Shigella can lead to bloody diarrhea followed by the often fatal hemolytic uremic syndrome (HUS). In the present paper, we aimed for a simple and effective toxin inhibitor by comparing three classes of carbohydrate-based inhibitors: glycodendrimers, glycopolymers, and oligosaccharides. We observed a clear enhancement in potency for multivalent inhibitors, with the divalent and tetravalent compounds inhibiting in the millimolar and micromolar range, respectively. However, the polymeric inhibitor based on galabiose was the most potent in the series exhibiting nanomolar inhibition. Alginate and chitosan oligosaccharides also inhibit Shiga toxin and may be used as a prophylactic drug during shigella outbreaks.

Citation

Diksha Haksar, Mostafa Asadpoor, Torben Heise, Jie Shi, Saskia Braber, Gert Folkerts, Lluis Ballell, Janneth Rodrigues, Roland J Pieters. Fighting Shigella by Blocking Its Disease-Causing Toxin. Journal of medicinal chemistry. 2021 May 13;64(9):6059-6069