Mannose-Presenting "Glyco-Colicins" Convert the Bacterial Cell Surface into a Multivalent Adsorption Site for...

Area of Science:

• Microbiology
• Biotechnology
• Drug Discovery

Background:

• Biofilm formation is a key factor in bacterial pathogenesis and antimicrobial resistance (AMR).
• Adherent-invasive *Escherichia coli* (AIEC) and uropathogenic *E. coli* (UPEC) utilize the FimH adhesin to bind mannose residues on host cells, contributing to diseases like inflammatory bowel disease and urinary tract infections.
• Existing mannose-based inhibitors face limitations due to monovalent interactions.

Purpose of the Study:

• To develop a novel non-bactericidal antiadhesion strategy against adherent bacteria.
• To overcome the limitations of monovalent carbohydrate-protein interactions in inhibiting bacterial adhesion.
• To explore the potential of bacterial surface receptors for multivalent display of functional motifs.

Main Methods:

• Preparation of colicin E9 bioconjugates engineered to bind the BtuB receptor on the bacterial outer membrane.
• Utilizing these bioconjugates for multivalent presentation of mannose motifs on the bacterial surface.
• Assessing the ability of mannose-presenting "glyco-colicins" to induce bacterial aggregation and inhibit FimH-mediated binding.

Main Results:

• The colicin E9 bioconjugates successfully labeled the surface of live *E. coli*.
• Mannose-presenting "glyco-colicins" were shown to induce *E. coli* aggregation.
• This bacterial aggregation effectively creates a multivalent mannose display platform, triggering binding to adjacent FimH-presenting bacteria.

Conclusions:

• This study pioneers a novel strategy using engineered bioconjugates to create a multivalent mannose display on bacteria via the BtuB receptor.
• The induced bacterial aggregation serves as an antiadhesion mechanism, offering a promising new avenue to combat AMR.
• This approach repurposes bacteria as a platform for therapeutic intervention, bypassing traditional inhibitor limitations.