# Convergent evolution of distinct D-ribulose utilisation pathways in attaching and effacing pathogens

**Authors:** Curtis Cottam, Kieran Bowran, Rhys T. White, Arnaud Baslé, Inokentijs Josts, James P. R. Connolly

PMC · DOI: 10.1038/s41467-025-62476-5 · Nature Communications · 2025-07-29

## TL;DR

This paper shows how two gut pathogens evolved different ways to use a sugar called D-ribulose, giving them a competitive edge in the gut.

## Contribution

The study reveals distinct and convergent D-ribulose utilization pathways in attaching and effacing pathogens, providing new mechanistic insights.

## Key findings

- EHEC uses the Aau transporter to import D-ribulose in the presence of L-arabinose, which is then metabolized via AraB.
- Citrobacter rodentium uses a dedicated D-ribulose transport and kinase system distinct from EHEC.
- Both pathogens have evolved convergent strategies to exploit D-ribulose for gut colonization.

## Abstract

Attaching and effacing pathogens overcome colonisation resistance by competing with metabolically similar organisms for limited resources. Enterohaemorrhagic E. coli (EHEC) utilises the pathogenicity island-encoded Accessory ʟ-arabinose Uptake (Aau) transporter to effectively colonise the mouse gut, hypothesised to be achieved via an enhanced capacity to scavenge ʟ-arabinose. Aau is regulated exclusively in response to ʟ-arabinose, but it is unclear how this system specifically benefits EHEC in vivo. Here, we show that Aau displays a > 200-fold higher affinity for the monosaccharide D-ribulose, over ʟ-arabinose. EHEC cannot grow on D-ribulose as a sole carbon source and this sugar does not trigger aau transcription. However, Aau effectively transports D-ribulose into the cell only in the presence of ʟ-arabinose, where it feeds into the pentose phosphate pathway, after phosphorylation by the ʟ-ribulokinase AraB, thus providing EHEC a significant fitness advantage. EHEC has therefore evolved a mechanism of hijacking the canonical ʟ-arabinose utilisation machinery to promote D-ribulose utilisation in vivo. Furthermore, Citrobacter rodentium encodes an analogous system that exclusively transports D-ribulose and metabolises it via a dedicated D-ribulokinase. These unique mechanisms of D-ribulose utilisation suggest that convergent evolution has driven the ability of distinct pathogenic species to exploit this nutrient during invasion of the gut niche.

Cottam et al. identify distinct pathways for D-ribulose utilisation in pathogenic Escherichia coli and Citrobacter rodentium, providing mechanistic details and suggesting convergent evolution towards utilisation of this nutrient in nature.

## Linked entities

- **Genes:** araB (L-ribulokinase) [NCBI Gene 913471]
- **Proteins:** araB (L-ribulokinase)
- **Chemicals:** D-ribulose (PubChem CID 151261), L-arabinose (PubChem CID 439195)
- **Species:** Citrobacter rodentium (taxon 67825), Mus musculus (taxon 10090)

## Full-text entities

- **Diseases:** EHEC (MESH:D004927), infection (MESH:D007239), inflammation (MESH:D007249), chronic (MESH:D002908), Aau (MESH:C536778), OI-17 (OMIM:615607)
- **Chemicals:** metal (MESH:D008670), SDS (MESH:D012967), lipids (MESH:D008055), glucuronate (MESH:D020723), AraB (MESH:D001089), Hydrogen (MESH:D006859), polysaccharides (MESH:D011134), Monosaccharide (MESH:D009005), nitrogen (MESH:D009584), PBS (MESH:D007854), Chloramphenicol (MESH:D002701), PEG 8000 (MESH:C000595216), D-galactose (MESH:D005690), PEG 1000 (MESH:C000595209), agar (MESH:D000362), streptomycin (MESH:D013307), AraC (MESH:D003561), D-xylose (MESH:D014994), amino acids (MESH:D000596), Kanamycin (MESH:D007612), MgCl2 (MESH:D015636), PEG400 (MESH:C000595213), polyol (MESH:C024617), ADP (MESH:D000244), luciferin (MESH:D000090562), pentose (MESH:D010429), Laemmli buffer (MESH:C088816), NaCl (MESH:D012965), ATP (MESH:D000255), pyruvate (MESH:D019289), sugar (MESH:D000073893), D-glucose (MESH:D005947), HEPES (MESH:D006531), Tween (MESH:D011136), ampicillin (MESH:D000667), D-ribose (MESH:D012266), pentose phosphate (MESH:D010428), ribitol (MESH:D012255), carbon (MESH:D002244), polystyrene (MESH:D011137), L-fucose (MESH:D005643), ADP-GloTM (-)
- **Species:** Escherichia fergusonii ATCC 35469 (strain) [taxon 585054], Bos taurus (bovine, species) [taxon 9913], Pseudescherichia vulneris (CDC Enteric Group 1, species) [taxon 566], Klebsiella aerogenes (species) [taxon 548], Citrobacter freundii (species) [taxon 546], Escherichia alba (species) [taxon 2562891], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Mus musculus (house mouse, species) [taxon 10090], Citrobacter rodentium ICC168 (strain) [taxon 637910], Escherichia coli (E. coli, species) [taxon 562], Citrobacter rodentium (species) [taxon 67825], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** ZAP193 — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_B2LM), E. coli BL21 (DE3) — Mus musculus (Mouse), Hybridoma (CVCL_B7HM), TUV93-0 — Homo sapiens (Human), Familial hypertrophic cardiomyopathy type 26, Induced pluripotent stem cell (CVCL_A6XE), M9 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_B417), pET28a — Oryctolagus cuniculus (Rabbit), Transformed cell line (CVCL_6E94)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12307932/full.md

## References

44 references — full list in the complete paper: https://tomesphere.com/paper/PMC12307932/full.md

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Source: https://tomesphere.com/paper/PMC12307932