Affiliation:
1. Department of Chemistry, University of Guelph, Guelph, ON, Canada
Abstract
A large number of children in the autism spectrum disorder suffer from gastrointestinal
(GI) conditions, such as constipation and diarrhea. Clostridium bolteae is a part of a set
of pathogens being regularly detected in the stool samples of hosts affected by GI and autism
symptoms. Accompanying studies have pointed out the possibility that such microbes affect
behaviour through the production of neurotoxic metabolites in a so-called, gut-brain connection.
As an extension of our Clostridium difficile polysaccharide (PS)-based vaccine research,
we engaged in the discovery of C. bolteae surface carbohydrates. So far, studies revealed that
C. bolteae produces a specific immunogenic PS capsule comprised of disaccharide repeating
blocks of mannose (Manp) and rhamnose (Rhap) units: α-D-Manp-(1→[-4)-β-D-Rhap-
(1→3)-α-D-Manp-(1→]n. For vaccinology and further immunogenic experiments, a method
to produce C. bolteae PS conjugates has been developed, along with the chemical syntheses
of the PS non-reducing end linkage, with D-Rha or L-Rha, α-D-Manp-(1→4)-α-D-Rhap-
(1→O(CH2)5NH2 and α-D-Manp-(1→4)-α-L-Rhap-(1→O(CH2)5NH2, equipped with an
aminopentyl linker at the reducing end for conjugation purposes. The discovery of C. bolteae
PS immunogen opens the door to the creation of non-evasive diagnostic tools to evaluate the
frequency and role of this microbe in autistic subjects and to a vaccine to reduce colonization
levels in the GI tract, thus impeding the concentration of neurotoxins.
Funder
Natural Sciences and Engineering Research Council (NSERC) Canada
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmacology,Molecular Medicine,Drug Discovery,Biochemistry,Organic Chemistry
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