# Mannose-Presenting “Glyco-Colicins” Convert the Bacterial Cell Surface into a Multivalent Adsorption Site for Adherent Bacteria

**Authors:** Natasha
E. Hatton, Joe Nabarro, Nicholas D. J. Yates, Alison Parkin, Laurence G. Wilson, Christoph G. Baumann, Martin A. Fascione

PMC · DOI: 10.1021/jacsau.4c00365 · JACS Au · 2024-06-12

## TL;DR

Researchers developed a new method using 'glyco-colicins' to prevent bacteria from sticking to surfaces, which could help combat antibiotic resistance.

## Contribution

The study introduces glyco-colicins as a novel antiadhesion strategy leveraging multivalent interactions.

## Key findings

- Glyco-colicins bind to E. coli and induce aggregation by presenting mannose on the bacterial surface.
- This approach uses bacteria as a platform to block adherence via FimH adhesin interactions.
- The method offers a nonbactericidal way to inhibit bacterial adhesion and potentially reduce infection risks.

## Abstract

Biofilm formation is integral to the pathogenesis of
numerous adherent
bacteria and contributes to antimicrobial resistance (AMR). The rising
threat of AMR means the need to develop novel nonbactericidal antiadhesion
approaches against such bacteria is more urgent than ever. Both adherent-invasive Escherichia coli (AIEC, implicated in inflammatory bowel
disease) and uropathogenic E. coli (UPEC, responsible
for ∼80% of urinary tract infections) adhere to terminal mannose
sugars on epithelial glycoproteins through the FimH adhesin on their
type 1 pilus. Although mannose-based inhibitors have previously been
explored to inhibit binding of adherent bacteria to epithelial cells,
this approach has been limited by monovalent carbohydrate–protein
interactions. Herein, we pioneer a novel approach to this problem
through the preparation of colicin E9 bioconjugates that bind to the
abundant BtuB receptor in the outer membrane of bacteria, which enables
multivalent presentation of functional motifs on the cell surface.
We show these bioconjugates label the surface of live E. coli and furthermore demonstrate that mannose-presenting “glyco-colicins”
induce E. coli aggregation, thereby using the bacteria,
itself, as a multivalent platform for mannose display, which triggers
binding to adjacent FimH-presenting bacteria.

## Linked entities

- **Proteins:** fimH (minor component of type 1 fimbriae), btuB (vitamin B12/cobalamin outer membrane transporter)
- **Chemicals:** mannose (PubChem CID 18950)
- **Diseases:** inflammatory bowel disease (MONDO:0005265)
- **Species:** Escherichia coli (taxon 562)

## Full-text entities

- **Genes:** colicin E9 [NCBI Gene 7377410]
- **Diseases:** urinary tract infections (MESH:D014552), inflammatory bowel disease (MESH:D015212)
- **Species:** Escherichia coli (E. coli, species) [taxon 562], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11200225/full.md

## References

59 references — full list in the complete paper: https://tomesphere.com/paper/PMC11200225/full.md

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Source: https://tomesphere.com/paper/PMC11200225