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Theses

Passage of botulinum neurotoxin across intestinal barrier

Abstract : paralysis, is produced by anaerobic bacteria of the Clostridium genus. BoNTs are classified into 7 types (A to G) and form different complexes by association with non-toxic proteins, including the non-toxic non-hemagglutinin component (NTNH) and hemagglutinins (HAs). En coding genes are clustered in the botulinum locus and organized in two divergent operons, ntnh-bont/A and ha34-ha17-ha70 for type A, whose expressions are positively regulated by the alternative sigma factor BotR. A synchronous expression peak of all the botulinum locus genes is measured by real-time RT-PCR at the transition between exponential and stationary growth phases, concomitantly to toxin accumulation in culture supernatant. In an intestinal epithelium model, purified BoNT/A is transcytosed after binding, via the Hc/A domain, to apical receptors including gangliosides and putative SV2-related proteins. Binding affinity and transport efficiency into intestinal cells are higher with crypt-type than with enterocytetype cell lines. Injected into the lumen of ligatured mouse ileal loops, BoNT/A inhibits smooth muscle contractions and fluorescent Hc/A migrates across mucosa, through some crypt cells, to submucosa and musculosa where it targets certain nerve endings, mostly cholinergic. Hc /A is internalized via different pathways into neuronal cells (dynamin- and clathrin-dependent) and intestinal cells (dynamin- and Cdc42-dependent, and clathrinindependent).
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https://pastel.archives-ouvertes.fr/pastel-00003461
Contributor : Ecole Agroparistech <>
Submitted on : Wednesday, February 27, 2008 - 8:00:00 AM
Last modification on : Wednesday, February 27, 2008 - 8:00:00 AM
Long-term archiving on: : Thursday, September 30, 2010 - 8:28:35 PM

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  • HAL Id : pastel-00003461, version 1

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Aurélie Couesnon. Passage of botulinum neurotoxin across intestinal barrier. Life Sciences [q-bio]. AgroParisTech, 2007. English. ⟨NNT : 2007AGPT0065⟩. ⟨pastel-00003461⟩

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