An antibacterial vaccination strategy based on a glycoconjugate containing the core lipopolysaccharide tetrasaccharide Hep2Kdo2

Nature Chemistry
Lingbing KongBenjamin G Davis

Abstract

Certain non-mammalian cell wall sugars are conserved across a variety of pathogenic bacteria. This conservation of structure, combined with their structural differences when compared with mammalian sugars, make them potentially powerful epitopes for immunization. Here, we report the synthesis of a glycoconjugate that displays the so-called 'inner core' sugars of Gram-negative bacterial cell walls. We also describe an antibacterial vaccination strategy based on immunization with the glycoconjugate and the subsequent administration of an inhibitor that uncovers the corresponding epitope in pathogenic bacteria. The core tetrasaccharide, Hep2Kdo2, a common motif in bacterial lipopolysaccharides, was synthesized and attached via a chain linker to a diphtheria toxin mutant carrier protein. This glycoconjugate generated titres of antibodies towards the inner core tetrasaccharide of the lipopolysaccharide, which were capable of binding the cell-surface sugars of bacterial pathogenic strains including Neisseria meningitidis, Pseudomonas aeruginosa and Escherichia coli. Exposure of bacterial lipopolysaccharide in in vitro experiments, using an inhibitor of capsular polysaccharide transport, enabled potent bacterial killing with antiserum.

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Citations

Feb 20, 2016·Nature Chemistry·David Bundle
Mar 17, 2018·FEMS Microbiology Reviews·Francesca MicoliRoberto Adamo
Jan 30, 2020·Nature Reviews. Microbiology·M Fata Moradali, Bernd H A Rehm
Dec 21, 2018·Current Opinion in Chemical Engineering·Kevin B WeyantMatthew P DeLisa
Apr 3, 2021·Drug Discovery Today·Scott S Walker, Todd A Black
Jul 17, 2018·Chemical Reviews·Liuqing WenPeng George Wang
Nov 26, 2020·The Journal of Organic Chemistry·Kwok-Kong Tony MongLi-Ching Shen
Aug 25, 2021·The Science of the Total Environment·Yu ShiHaiyan Chu
Sep 9, 2021·Biochemical Society Transactions·Magdalena E ZasłonaOren Moscovitz

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