Glycolipid receptor depletion as an approach to specific antimicrobial therapy

FEMS Microbiology Letters
Majlis SvenssonCatharina Svanborg

Abstract

Mucosal pathogens recognize glycoconjugate receptors at the site of infection, and attachment is an essential first step in disease pathogenesis. Inhibition of attachment may prevent disease, and several approaches have been explored. This review discusses the prevention of bacterial attachment and disease by agents that modify the glycosylation of cell surface glycoconjugates. Glycosylation inhibitors were tested in the urinary tract infection model, where P-fimbriated Escherichia coli rely on glycosphingolipid receptors for attachment and tissue attack. N-butyldeoxynojirimycin blocked the expression of glucosylceramide-derived glycosphingolipids and attachment was reduced. Bacterial persistence in the kidneys was impaired and the inflammatory response was abrogated. N-butyldeoxynojirimycin was inactive against strains which failed to engage these receptors, including type 1 fimbriated or nonadhesive strains. In vivo attachment has been successfully prevented by soluble receptor analogues, but there is little clinical experience of such inhibitors. Large-scale synthesis of complex carbohydrates, which could be used as attachment inhibitors, remains a technical challenge. Antibodies to bacterial lectins involved in attachment m...Continue Reading

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Citations

Sep 13, 2011·Current Opinion in Biotechnology·Caterina SignorettoCarla Pruzzo
May 17, 2011·Chemistry and Physics of Lipids·Thomas Kolter
Jul 1, 2008·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Anu M KanteleJussi M Kantele
Nov 27, 2015·Genetics, Selection, Evolution : GSE·Edin HamzićBertrand Bed'Hom
Jun 27, 2013·Virulence·Anne Marie Krachler, Kim Orth
Mar 2, 2016·Pathogens·Gabriela GodalyCatharina Svanborg
Oct 3, 2018·Infection·Arezoo AsadiMehrdad Gholami
Aug 3, 2019·ACS Infectious Diseases·Allison C LeonardGeorgina Cox

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