Gut mucin fucosylation dictates the entry of botulinum toxin complexes.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41290571.
- Also identified by DOI 10.1038/s41467-025-65384-w and PMC identifier 12647801.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Botulinum toxins (BoNTs) produced by Clostridium botulinum are the most potent known bacterial toxins. The BoNT complex from serotype B-Okra (LPTC/B<sup>Okra</sup>) exerts at least 80-fold higher oral toxicity in mice compared with that from serotype A1 (L-PTC/A<sup>62A</sup>). Here, we show that L-PTC/B<sup>Okra</sup> is predominantly absorbed through enterocytes, whereas LPTC/A<sup>62A</sup> targets intestinal microfold cells. Furthermore, α1,2-fucosylation of intestinal mucin determines the oral toxicity of L-PTCs as well as their entry routes, due to differential carbohydrate-binding spectrum of one of the L-PTC components, the hemagglutinin (HA) complex. Fucosylation-deficient mice display reduced intestinal mucin penetration of L-PTC/B<sup>Okra</sup> via HA, and lower susceptibility to oral intoxication with this toxin. Thus, our results shed light on the molecular mechanisms by which the oral toxicity of BoNTs is increased after crossing intestinal mucus layers.
Medical subject headings
- Mucins
- Intestinal Mucosa
- Botulinum Toxins
- Fucose
- Botulinum Toxins, Type A