Cited by 0Escherichia coli research studiesBacterial Genetics and BiotechnologyEnterobacteriaceae and Cronobacter Research

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

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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.

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Research works printed but not linked: 58

  1. Croxen, M. A. & Finlay, B. B. Molecular mechanisms of Escherichia coli pathogenicity. Nat. Rev. Microbiol. 8, 26–38 (2010). · DOI
  2. Deng, W. et al. Assembly, structure, function and regulation of type III secretion systems. Nat. Rev. Microbiol. 15, 323–337 (2017). · DOI
  3. Coulthurst, S. The type VI secretion system: a versatile bacterial weapon. Microbiology 165, 503–515 (2019). · DOI
  4. Conway, T. & Cohen, P. S. Commensal and pathogenic Escherichia coli metabolism in the Gut. Microbiol. Spectr. 3, 10 (2015). · DOI
  5. Thomas, C. & Tampé, R. Structural and mechanistic principles of ABC transporters. Annu. Rev. Biochem. 89, 605–636 (2020). · DOI
  6. Davidson, A. L., Dassa, E., Orelle, C. & Chen, J. Structure, function, and evolution of bacterial ATP-binding cassette systems. Microbiol. Mol. Biol. Rev. 72, 317–364 (2008). · DOI
  7. Maqbool, A. et al. The substrate-binding protein in bacterial ABC transporters: dissecting roles in the evolution of substrate specificity. Biochem. Soc. Trans. 43, 1011–1017 (2015). · DOI
  8. Shea, A. E. et al. Emerging roles for ABC transporters as virulence factors in uropathogenic Escherichia coli. Proc. Natl. Acad. Sci. USA 121, e2310693121 (2024). · DOI
  9. Perna, N. T. et al. Genome sequence of enterohaemorrhagic Escherichia coli O157:H7. Nature 409, 529–533 (2001). · DOI
  10. Welch, R. A. et al. Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli. Proc. Natl. Acad. Sci. USA 99, 17020–17024 (2002). · DOI
  11. Sintsova, A. et al. Genetically diverse uropathogenic Escherichia coli adopt a common transcriptional program in patients with UTIs. Elife 8, e49748 (2019). · DOI
  12. Frick-Cheng, A. E. et al. The gene expression profile of uropathogenic Escherichia coli in women with uncomplicated urinary tract infections is recapitulated in the mouse model. mBio 11, e01412–e01420 (2020). · DOI
  13. Bielecki, P. et al. In Vivo mRNA profiling of uropathogenic Escherichia coli from diverse phylogroups reveals common and group-specific gene expression profiles. mBio 5, e01075–e01014 (2014). · DOI
  14. Subashchandrabose, S. et al. Host-specific induction of Escherichia coli fitness genes during human urinary tract infection. Proc. Natl. Acad. Sci. USA 111, 18327–18332 (2014). · DOI
  15. Connolly, J. P. R. et al. Host-associated niche metabolism controls enteric infection through fine-tuning the regulation of type 3 secretion. Nat. Commun. 9, 4187 (2018). · DOI
  16. Cottam, C. et al. Metabolism of l-arabinose converges with virulence regulation to promote enteric pathogen fitness. Nat. Commun. 15, 4462 (2024). · DOI
  17. Wale, K. R. et al. A master regulator of central carbon metabolism directly activates virulence gene expression in attaching and effacing pathogens. PLoS Pathog. 20, e1012451 (2024). · DOI
  18. Kamada, N. et al. Regulated virulence controls the ability of a pathogen to compete with the gut microbiota. Science 336, 1325–1329 (2012). · DOI · Paper page
  19. Crepin, V. F., Collins, J. W., Habibzay, M. & Frankel, G. Citrobacter rodentium mouse model of bacterial infection. Nat. Protoc. 11, 1851–1876 (2016). · DOI
  20. Mullineaux-Sanders, C. et al. Citrobacter rodentium–host–microbiota interactions: immunity, bioenergetics and metabolism. Nat. Rev. Microbiol. 17, 701–715 (2019). · DOI
  21. Collins, J. W. et al. Citrobacter rodentium: infection, inflammation and the microbiota. Nat. Rev. Microbiol. 12, 612–623 (2014). · DOI
  22. Wale, K. R., Cottam, C., Connolly, J. P. & Roe, A. J. Transcriptional and metabolic regulation of EHEC and citrobacter rodentium pathogenesis. Curr. Opin. Microbiol. 63, 70–75 (2021). · DOI
  23. Schleif, R. AraC protein, regulation of the l-arabinose operon in Escherichia coli, and the light switch mechanism of AraC action. FEMS Microbiol. Rev. 34, 779–796 (2010). · DOI
  24. Singh, C., Glaab, E., Linster, C. L. & Denu, J. M. Molecular identification of D-ribulokinase in budding yeast and mammals. J. Biol. Chem. 292, 1005–1028 (2017). · DOI
  25. Lee, L. V., Gerratana, B. & Cleland, W. W. Substrate specificity and kinetic mechanism of Escherichia coli ribulokinase. Arch. Biochem. Biophys. 396, (2001). · DOI
  26. Elsinghorst, E. A. & Mortlock, R. P. Molecular cloning of the Escherichia coli B L-fucose-D-arabinose gene cluster. J. Bacteriol. 176, (1994). · DOI
  27. Neuberger, M. S., Hartley, B. S. & Walker, J. E. Purification and properties of D-ribulokinase and D-xylulokinase from Klebsiella aerogenes. Biochem. J. 193, 513–524 (1981). · DOI
  28. Heuel, H., Shakeri-Garakani, A., Turgut, S. & Lengeler, J. W. Genes for D-arabinitol and ribitol catabolism from Klebsiella pneumoniae. Microbiology 144, 1631–1639 (1998). · DOI
  29. Freter, R., Brickner, H., Fekete, J., Vickerman, M. M. & Carey, K. E. Survival and implantation of Escherichia coli in the intestinal tract. Infect. Immun. 39, 686–703 (1983). · DOI · Paper page
  30. Meador, J. P., Caldwell, M. E., Cohen, P. S. & Conway, T. Escherichia coli pathotypes occupy distinct niches in the mouse intestine. Infect. Immun. 82, 1931–1938 (2014). · DOI
  31. Yip, A. Y. G. et al. Antibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites. Nat. Commun. 14, 5094 (2023). · DOI · Paper page
  32. Liu, B. et al. Enterohaemorrhagic E. coli utilizes host- and microbiota-derived L-malate as a signaling molecule for intestinal colonization. Nat. Commun. 14, 7227 (2023). · DOI
  33. Zhang, J., Zhang, Y., Xia, Y. & Sun, J. Imbalance of the intestinal virome and altered viral-bacterial interactions caused by a conditional deletion of the vitamin D receptor. Gut Microbes 13, 5094 (2021). · DOI
  34. Robinson, A. M. et al. Fecal microbiota and metabolome in a mouse model of spontaneous chronic colitis: relevance to human inflammatory bowel disease. Inflamm Bowel Dis. 22, 2767–2787 (2016). · DOI
  35. Brown, D. G. et al. Metabolomics and metabolic pathway networks from human colorectal cancers, adjacent mucosa, and stool. Cancer Metab. 4, 11 (2016). · DOI
  36. Koirala, S., Wang, X. & Rao, C. V. Reciprocal regulation of L-arabinose and D-xylose metabolism in Escherichia coli. J. Bacteriol. 198, 386–393 (2016). · DOI
  37. Ammar, E. M., Wang, X. & Rao, C. V. Regulation of metabolism in Escherichia coli during growth on mixtures of the non-glucose sugars: arabinose, lactose, and xylose. Sci. Rep. 8, 609 (2018). · DOI
  38. Murray, C. J. et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 399, 629–655 (2022). · DOI · Paper page
  39. Beisel, C. L. & Afroz, T. Rethinking the hierarchy of sugar utilization in bacteria. J. Bacteriol. 198 https://doi.org/10.1128/JB.00890-15 (2015). · DOI
  40. Desai, T. A. & Rao, C. V. Regulation of arabinose and xylose metabolism in Escherichia coli. Appl Environ. Microbiol. 76, 1524–1532 (2010). · DOI
  41. Mauzy, C. A. & Hermodson, M. A. Structural and functional analyses of the repressor, RbsR, of the ribose operon of Escherichia coli. Protein Sci. 1, 831–842 (1992). · DOI
  42. Chen, Y. M., Tobin, J. F., Zhu, Y., Schleif, R. F. & Lin, E. C. Cross-induction of the L-fucose system by L-rhamnose in Escherichia coli. J. Bacteriol. 169, 3712–3719 (1987). · DOI
  43. Datsenko, K. A. & Wanner, B. L. One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc. Natl. Acad. Sci. USA 97, 6640–6645 (2000). · DOI
  44. Evans, P. R. & Murshudov, G. N. How good are my data and what is the resolution? Acta Crystallogr. D Biol. Crystallogr. 69, 1204–1214 (2013). · DOI
  45. Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66, 486–501 (2010). · DOI · Paper page
  46. Murshudov, G. N. et al. REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr. D Biol. Crystallogr. 67, 355–367 (2011). · DOI
  47. Liebschner, D. et al. Polder maps: improving OMIT maps by excluding bulk solvent. Acta Crystallogr. D Struct. Biol. 73, 148–157 (2017). · DOI
  48. Eberhardt, J., Santos-Martins, D., Tillack, A. F. & Forli, S. AutoDock vina 1.2.0: new docking methods, expanded force field, and Python bindings. J. Chem. Inf. Model. 61, 3891–3898 (2021). · DOI
  49. Moriarty, N. W., Grosse-Kunstleve, R. W. & Adams, P. D. Electronic ligand builder and optimization workbench (eLBOW): a tool for ligand coordinate and restraint generation. Acta Crystallogr. D Biol. Crystallogr. 65, 1074–1080 (2009). · DOI
  50. Almagro Armenteros, J. J. et al. SignalP 5.0 improves signal peptide predictions using deep neural networks. Nat. Biotechnol. 37, 420–423 (2019). · DOI
  51. Paysan-Lafosse, T. et al. InterPro in 2022. Nucleic Acids Res. 51, D418–D427 (2023). · DOI
  52. Chen, I. M. A. et al. IMG/M v.5.0: an integrated data management and comparative analysis system for microbial genomes and microbiomes. Nucleic Acids Res. 47, D666–D677 (2019). · DOI
  53. Edgar, R. C. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 32, 1792–1797 (2004). · DOI · Paper page
  54. Tamura, K., Stecher, G. & Kumar, S. MEGA11: molecular evolutionary genetics analysis version 11. Mol. Biol. Evol. 38, 3022–3027 (2021). · DOI
  55. Achtman, M., Zhou, Z., Charlesworth, J. & Baxter, L. EnteroBase: hierarchical clustering of 100,000s of bacterial genomes into species/subspecies and populations. Philos. Trans. R Soc. Lond B Biol. Sci. 377, 20210240 (2022). · DOI
  56. Zhou, Z., Alikhan, N. F., Mohamed, K., Fan, Y. & Achtman, M. The EnteroBase user’s guide, with case studies on Salmonella transmissions, Yersinia pestis phylogeny, and Escherichia core genomic diversity. Genome Res 30, 20210240 (2020). · DOI
  57. Berman, H. M. et al. The Protein Data Bank. Nucleic Acids Res. 28, 235–242 (2000). · DOI · Paper page
  58. Yariv, B. et al. Using evolutionary data to make sense of macromolecules with a “face-lifted” ConSurf. Protein Sci. 32, e4582 (2023). · DOI

Metadata

Authors
Cottam, C., Bowran, K., White, R. T., Baslé, A., Josts, I., & Connolly, J. P. R.
Affiliations
  • Newcastle University (GB)
  • New Zealand Institute for Public Health and Forensic Science (NZ)
Corresponding author
Connolly, James P. R.
Venue
Nature Communications
Published
2025-07-29
Volume
16
Issue
1
Pages
6976-6976
ISSN
2041-1723 (ISSN-L)
OpenAlex
W4412785781
Cited by
0
References
5
FWCI
0.00
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • Newcastle University ePrints (Newcastle Univesity) (cc-by)
Funders
  • Academy of Medical Sciences (SBF005\1029)
  • RCUK | Medical Research Council (MR/X007197/1)
  • Royal Society (RGS\R2\202100, URF\R1\231752)
Topics
  • Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Immunology and Microbiology › Microbiology › Enterobacteriaceae and Cronobacter Research
Keywords
convergent evolution, attaching and effacing pathogens, enterohemorrhagic Escherichia coli, Citrobacter rodentium, pentose phosphate pathway, colonization resistance, nutrient competition, sugar transporters
MeSH terms
Animals, Arabinose, Humans, Pentose Phosphate Pathway, Gene Expression Regulation, Bacterial, Evolution, Molecular, Escherichia coli Proteins, Citrobacter rodentium, Mice, Enterohemorrhagic Escherichia coli

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