Targeting catecholate siderophore systems enables precision depletion of gut enterobacteria during colitis

Authors

Norton, G. J., Dudek, A. M., Gerner, R. R., Guo, C., Castillo, V., Argueta, F. A., Beebout, C. J., Kanyabi, G., Drushell, J., Walker, G. T., Hsu, C.-Y., Bessho, S., Nuccio, S.-P., Chu, H., Zengler, K., Nolan, E. M., Raffatellu, M.

Abstract

Adherent-invasive Escherichia coli (AIEC) is frequently isolated from the dysbiotic gut microbiome in inflammatory bowel disease and is implicated in disease progression, highlighting its potential as a therapeutic target. Here we show that iron acquisition is essential for AIEC colonization of the inflamed gut. Mechanistically, four catecholate siderophore receptors act redundantly to support AIEC growth under iron-limited conditions and during colitis. Immunization of colitis-prone Il10-/- mice against catecholate siderophores reduced intestinal AIEC colonization, particularly its association with the mucosa, while largely preserving overall gut microbiome composition. Longitudinal metagenomic profiling identified immunization-associated shifts in Akkermansiaceae and Lactobacillaceae, and experiments in gnotobiotic Il10-/- mice demonstrated that Limosilactobacillus reuteri, a member of the Lactobacillaceae, limited AIEC colonization, whereas Akkermansiaceae exacerbated disease. Our findings establish catecholate siderophore-mediated iron acquisition as a therapeutic target in AIEC and provide proof-of-principle that virulence-targeted immunization can selectively antagonize a disease-associated bacterium while preserving the gut microbiota

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 06 Oct 2026.

Stats

1-terrible, 9-excellent. How would you rate this preprint? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.