BabA and LPS inhibitors against Helicobacter pylori: pectins and pectin-like rhamnogalacturonans as adhesion blockers
The first step in the development of Helicobacter pylori pathogenicity is receptor-mediated adhesion to gastric epithelium. Adhesins of H. pylori not only enable colonisation of the epithelium, with BabA interacting with Lewisb, but also interaction of lipopolysaccharide (LPS) with galectin-3 contributes to attachment of H. pylori to the host cells. Anti-adhesive compounds against H. pylori have been described, but specific analytical assays for pinpointing the interaction with BabA are limited. LPS-galectin-3 inhibitors have not been described until now. A sandwich ELISA with recombinant BabA547-6K was developed to investigate the interaction of BabA with Lewisb-HSA. Isothermal titration calorimetry gave thermodynamic information on the interaction between BabA, Lewisb-HSA and anti-adhesive compounds. A highly esterified rhamnogalacturonan from Abelmoschus esculentus inhibited the adhesion of H. pylori to adherent gastric adenocarcinoma (AGS) cells (IC50 550 μg/mL) and interacted with BabA (IC50 17 μg/mL). Pectins with similar rhamnogalacturonan structure showed weak anti-adhesive activity. Highly branched rhamnogalacturonans with low uronic acid content and high degree of esterification are potent BabA inhibitors. BabA represents a promising target for the development of anti-adhesive drugs against H. pylori. The rhamnogalacturonan influenced also the binding affinity of H. pylori to recombinant galectin-3 in a concentration-dependent manner with an IC50 of 222 μg/mL. Similar effects were obtained with pectin from apple fruits, while pectins from other sources were inactive.
KeywordsAdhesion Helicobacter pylori BabA Lipopolysaccharide Okra Pectin Rhamnogalacturonan
The authors would like to thank Geoffrey A. Holdgate (AstraZeneca) for his help with ITC experiments.
MG was partially funded by a Boehringer Ingelheim Fonds travel grant (no special grant number available) and by the Apothekerstiftung Westfalen-Lippe (no special grant number available). VP and FHF were funded through EPSRC (Grant EP/L01646X) and AstraZeneca R&D as part of the CDT for Advanced Therapeutics and Nanomedicines.
MG performed experiments and made substantial contributions to acquisition, analysis and interpretation of data; VP performed ITC experiments and contributed to MS; AM supported with experiments; FHF was involved in experiments, revised and discussed the MS; AH designed the study and has been involved in drafting and revising the MS
Compliance with Ethical Standards
This article does not contain studies with human participants performed by any of the authors.
Conflict of Interest
The authors declare that they have no conflict of interest.
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