Glycodendrimers as anti-adhesion drugs against type 1 fimbriated E. coli uropathogenic infections

Bacterial drug resistance against antimicrobial agents is a prevalent and central worldwide impasse. Infections with resistant organisms lead to adverse clinical outcomes, increased mortality, and are costly to healthcare systems. Several infectious diseases are initiated by the binding of pathogenic lectins to host cells glycoconjugates. The molecular understanding of these adhesion phenomena is crucial and presents promising new alternatives compared to traditional antibiotic therapies. Glycans or glycan mimetics could be used to inhibit the initial recognition events leading to adhesion and colonization of host tissues by pathogens. The bladder and urothelial lining are widely covered by cell surface glycoproteins bearing the required carbohydrate ligands responsible for the adhesion phenomena. However, when these interactions are measured on a per saccharide basis, they are generally too weak (mM) for the design of beneficial inhibition therapies. The interactions between microbial pathogens and host cells are often governed by polyvalent and overall strong avidities. To overcome this drawback, glycobiologists have design a new family of well-defined small macromolecules, called glycodendrimers that can successfully address this issue. This review will provide a brief introduction on glycodendrimers and detailed descriptions of design and applications of mannosylated inhibitors against fimbriated type 1 E. coli.