Targeting catecholate siderophore systems enables precision depletion of gut enterobacteria during colitis
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…
Gut bacteria known as adherent-invasive Escherichia coli (AIEC) have been linked to inflammatory bowel disease and may contribute to its worsening. Researchers have discovered that these bacteria rely on iron acquisition to colonize inflamed guts. Four catecholate siderophore receptors work together to enable AIEC growth in iron-limited environments during colitis.
A study in colitis-prone Il10-/- mice showed that immunization against catecholate siderophores led to reduced AIEC colonization, particularly on the mucosa, while mostly maintaining the overall gut microbiome composition. Analysis of gut microbiota over time revealed changes in the abundance of Akkermansiaceae and Lactobacillaceae.
In experiments with gnotobiotic Il10-/- mice, Limosilactobacillus reuteri, a member of the Lactobacillaceae family, was found to limit AIEC colonization, while Akkermansiaceae worsened the condition. These findings suggest that targeting the catecholate siderophore-mediated iron acquisition pathway could be a potential therapeutic approach for AIEC, and that virulence-targeted immunization may selectively inhibit a disease-associated bacterium while preserving the gut microbiota.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
