---
title: "Targeting catecholate siderophores to deplete gut Enterobacteria during colitis"
id: "biorxiv-22-targeting-catecholate-siderophore-systems-enables-precision-depletion-of-gut"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-22-targeting-catecholate-siderophore-systems-enables-precision-depletion-of-gut"
content_type: "clinical_feed_article"
specialty: "Gastroenterology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.02.756324v1?rss=1"
published_at: "2026-10-05T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Targeting catecholate siderophores to deplete gut Enterobacteria during colitis
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-22-targeting-catecholate-siderophore-systems-enables-precision-depletion-of-gut
- **Specialty:** [Gastroenterology](https://medichelpline.com/clinical-feed/gastroenterology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.02.756324v1?rss=1)
- **Published At:** 2026-10-05T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Adherent-invasive Escherichia coli (**AIEC**) is commonly found in the dysbiotic gut microbiome of inflammatory bowel disease and contributes to disease progression, making it a potential therapeutic target. - The study reports that **iron acquisition** is essential for AIEC colonization of the inflamed gut; blocking iron uptake impairs AIEC growth under iron-limited conditions and during colitis. - Four **catecholate siderophore** receptors function redundantly to support AIEC growth, indicating multiple iron-uptake pathways contribute to its fitness in the inflamed intestine. - Active immunization against catecholate siderophores in colitis-prone **Il10-/- mice** reduced intestinal AIEC colonization and particularly decreased AIEC association with the mucosa, while largely preserving overall gut microbiome composition. - Longitudinal metagenomic profiling after immunization revealed shifts in the abundances of **Akkermansiaceae** and **Lactobacillaceae** families. - Gnotobiotic Il10-/- mouse experiments identified **Limosilactobacillus reuteri** (a Lactobacillaceae member) as limiting AIEC colonization, whereas members of **Akkermansiaceae** exacerbated disease in this model. - Findings support **catecholate siderophore-mediated iron acquisition** as a therapeutic target for AIEC and provide proof-of-principle that virulence-targeted immunization can selectively antagonize a disease-associated bacterium while preserving the gut microbiota. - Competing interest: K. Zengler is cofounder of Guilden Corporation; other authors reported no competing interests. Funding sources were declared but specific additional details beyond listed grants were not reported in the abstract.
## Clinical Analysis & Structured Key Points
Targeting catecholate siderophore systems enables precision depletion of gut enterobacteria during colitis | bioRxiv Skip to main content New Results Targeting catecholate siderophore systems enables precision depletion of gut enterobacteria during colitis Grant J. Norton , Anna M. Dudek , Romana R. Gerner , Chuchu Guo , Vanessa Castillo , Felix A. Argueta , Connor J. Beebout , Ghazal Kanyabi , Julia Drushell , Gregory T. Walker , Chia-Yun Hsu , Shingo Bessho , Sean-Paul Nuccio , Hiutung Chu , Karsten Zengler , Elizabeth M. Nolan , Manuela Raffatellu doi: https://doi.org/10.64898/2026.10.02.756324 Grant J. Norton 1 University of California, San Diego; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Anna M. Dudek 1 University of California, San Diego; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Romana R. Gerner 1 University of California, San Diego; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Chuchu Guo 2 Massachusetts Institute of Technology Find this author on Google Scholar Find this author on PubMed Search for this author on this site Vanessa Castillo 1 University of California, San Diego; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Felix A. Argueta 1 University of California, San Diego; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Connor J. Beebout 1 University of California, San Diego; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ghazal Kanyabi 2 Massachusetts Institute of Technology Find this author on Google Scholar Find this author on PubMed Search for this author on this site Julia Drushell 1 University of California, San Diego; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Gregory T. Walker 1 University of California, San Diego; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Chia-Yun Hsu 1 University of California, San Diego; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Shingo Bessho 1 University of California, San Diego; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Sean-Paul Nuccio 1 University of California, San Diego; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Hiutung Chu 1 University of California, San Diego; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Karsten Zengler 1 University of California, San Diego; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Elizabeth M. Nolan 2 Massachusetts Institute of Technology Find this author on Google Scholar Find this author on PubMed Search for this author on this site Manuela Raffatellu 1 University of California, San Diego; Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: manuelar{at}ucsd.edu Abstract Info/History Metrics Supplementary material Preview PDF 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 Competing Interest Statement K. Zengler is cofounder of Guilden Corporation, a company developing treatments to increase drug efficacy. All other authors declare that they have no competing interests. Funder Information Declared National Institutes of Health , F31AI186410 , T32AI007036 , R01AI176390 , R37AI126277 , R21AI186034 , R01AI167860 Max Kade Foundation, https://ror.org/02tn5vs15 Crohn's and Colitis Foundation , 649744 Japan Agency for Medical Research and Development , JP233fa627004 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Back to top Previous Next Posted October 05, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Targeting catecholate siderophore systems enables precision depletion of gut enterobacteria during colitis Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Targeting catecholate siderophore systems enables precision depletion of gut enterobacteria during colitis Grant J. Norton , Anna M. Dudek , Romana R. Gerner , Chuchu Guo , Vanessa Castillo , Felix A. Argueta , Connor J. Beebout , Ghazal Kanyabi , Julia Drushell , Gregory T. Walker , Chia-Yun Hsu , Shingo Bessho , Sean-Paul Nuccio , Hiutung Chu , Karsten Zengler , Elizabeth M. Nolan , Manuela Raffatellu bioRxiv 2026.10.02.756324; doi: https://doi.org/10.64898/2026.10.02.756324 Share This Article: Copy Citation Tools Targeting catecholate siderophore systems enables precision depletion of gut enterobacteria during colitis Grant J. Norton , Anna M. Dudek , Romana R. Gerner , Chuchu Guo , Vanessa Castillo , Felix A. Argueta , Connor J. Beebout , Ghazal Kanyabi , Julia Drushell , Gregory T. Walker , Chia-Yun Hsu , Shingo Bessho , Sean-Paul Nuccio , Hiutung Chu , Karsten Zengler , Elizabeth M. Nolan , Manuela Raffatellu bioRxiv 2026.10.02.756324; doi: https://doi.org/10.64898/2026.10.02.756324 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (8083) Biochemistry (18888) Bioengineering (15042) Bioinformatics (44830) Biophysics (22761) Cancer Biology (19887) Cell Biology (27093) Clinical Trials (138) Developmental Biology (14050) Ecology (21186) Epidemiology (2067) Evolutionary Biology (25612) Genetics (16254) Genomics (23643) Immunology (18840) Microbiology (42796) Molecular Biology (18197) Neuroscience (94226) Paleontology (706) Pathology (3009) Pharmacology and Toxicology (5137) Physiology (8187) Plant Biology (16110) Scientific Communication and Education (2101) Synthetic Biology (4597) Systems Biology (10306) Zoology (2402)
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