Inhibition of bacterial adhesion to live human cells: Activity and cytotoxicity of synthetic mannosides

Abstract

Edited by Renee TsolisKeywords: Bacterial adhesion a-Mannoside inhibitor HT-29 cell Cytotoxicity Anti-adhesion therapy Type 1 fimbriated E. coli a b s t r a c t Bacterial adhesion to glycosylated surfaces is a key issue in human health and disease. Inhibition of bacterial adhesion by suitable carbohydrates could lead to an anti-adhesion therapy as a novel approach against bacterial infections. A selection of five a-mannosides has been evaluated as inhibitors of bacterial adhesion to the polysaccharide mannan, as well as to the surface of live human HT-29 cells. Cell toxicity studies were performed to identify the therapeutic window for a potential in vivo-application of the tested carbohydrates. A previously published mannosidic squaric acid diamide was shown to be exceptionally effective as inhibitor of the bacterial lectin FimH.

Increasing bacterial affinity and cytocompatibility with four-arm star glycopolymers and antimicrobial α-polylysine

“…In order to investigate the enhanced binding affinity contributed by the pendant mannose moieties, the MIC of linear P(Lys) and the P(ManEMA) 10 -P(Lys) conjugate was tested in the presence of methyl α-D-mannopyranoside (MeMan), a nanomolar FimH antagonist. 40,41 There is no difference in the MIC value of the linear P(Lys), regardless of the presence of MeMan (Fig. 3).…”

Polybacterial human disease: the ills of social networking

“…Adhesion inhibitors based on synthetic receptor analogs have also proved to be potent in disrupting adhesion of many bacteria [61]. For example, synthetic peptides and glycerophosphate derivatives mimicking fragments of fimbrial adhesins have been effective against several oral infection studies of mice [61].…”

“…For example, synthetic peptides and glycerophosphate derivatives mimicking fragments of fimbrial adhesins have been effective against several oral infection studies of mice [61]. Although these studies provide evidence of the potential of adhesion inhibitors, the use of these molecules in their present form is not desirable owing to their proinflammatory properties and potential cytotoxicity.…”

Anti-virulence Strategies to Target Bacterial Infections

“…Biphenyl mannosides were shown to be 200,000 fold more potent than the originally tested monovalent mannose. The substances are orally available and demonstrate an overall low toxicity (Han et al 2012;Hartmann et al 2012). Additionally, mouse models indicate that biphenyl mannosides decrease colonization levels significantly (Klein et al 2010).…”