Structure and synthesis of a vaccine and diagnostic target for Enterocloster bolteae, an autism-associated gut pathogen – Part II. (April 2023)

• Record Type: Journal Article
• Authors: Frame, Nolan W.; Allas, Mikel Jason; Pequegnat, Brittany; Vinogradov, Evguenii; Liao, Victor C.-H.; Al-Abdul-Wahid, Sameer; Arroyo, Luis; Allen-Vercoe, Emma; Lowary, Todd L.; Monteiro, Mario A.
• Is Part Of: Carbohydrate research. Volume 526(2023)
• Publication Date: 2023-04
• Subjects: Enterocloster bolteae -- Clostridium bolteae -- Autism: diarrhea: microbiome -- Polysaccharide; Carbohydrates -- Periodicals; Chemistry, Organic -- Periodicals; Biochemistry -- Periodicals; Carbohydrates -- Periodicals; Chimie organique -- Périodiques; Glucides -- Périodiques; Biochemistry; Carbohydrates; Chemistry, Organic; Periodicals; Electronic journals; 507.78
• DOI: 10.1016/j.carres.2023.108805
• Languages: English
• ISSNs: 0008-6215

Abstract

Abstract: Enterocloster bolteae (formerly known as Clostridium bolteae ) is a gastro-intestinal pathogenic bacterium often detected in the fecal microbiome of children in the autism spectrum. E. bolteae excretes metabolites that are thought to act as neurotoxins. This study is an update of our first E. bolteae investigation that discovered an immunogenic polysaccharide. Through a combination of chemical derivatizations/degradations, spectrometry and spectroscopy techniques, a polysaccharide composed of disaccharide repeating blocks comprised of 3-linked β-d -ribofuranose and 4-linked α-l -rhamnopyranose, [→3)-β-D-Rib f -(1 → 4)-α-L-Rha p -(1→]n, was identified. To confirm the structure, and to provide material for subsequent investigations, the chemical synthesis of a corresponding linker-equipped tetrasaccharide, β-D-Rib f -(1 → 4)-α-L-Rha p -(1 → 3)-β-D-Rib f -(1 → 4)-α-L-Rha p -(1→O(CH2 )8 N3, is also described. Research tools based on this immunogenic glycan structure can form the foundation for serotype classification, diagnostic/vaccine targets and clinical studies into the hypothesized role of E. bolteae in the onset/augmentation of autism related conditions in children. Graphical abstract: Image 1 Highlights: A polysaccharide formed by [.→3)-β-D-Rib f -(1 → 4)-α-L-Rha p -(1→] disaccharide repeats was isolated from the gut pathogen, Enterocloster bolteae (formerly Clostridium bolteae ) . The chemical synthesis of a linker-equipped tetrasaccharide containing two repeating blocks, β-D-Rib f -(1. → 4)-α-L-Rha p -(1 → 3)-β-D-Rib f -(1 → 4)-α-L-Rha p -(1→O(CH2)8N3, was achieved. This work rectifies a previous proposed polysaccharide structure of Clostridium bolteae strain 16351.