The accessory type III secretion system effectors collectively shape intestinal inflammatory infection outcomes
Author(s)
Type
Journal Article
Abstract
Injection of effectors via a type III secretion system (T3SS) is an infection strategy shared by various Gram-negative bacterial pathogens, many infecting mucosal surfaces. While individual T3SS effectors are well characterized, their network-level organization and the distinction between core and accessory effectors remain incompletely understood. Here, by systematically dissecting the T3SS effector network of the enteric mouse pathogen Citrobacter rodentium (CR) we identified a subset of 12 accessory effectors that, while dispensable for colonization, significantly alter infection outcomes. A strain lacking the accessory effectors (CRM12) remained virulent in susceptible mouse hosts yet resulted in reduced epithelial barrier damage, inflammation, and immune cell infiltration in resistant mice. Deep proteomic analysis specifically targeting CR-attached colonic epithelial cells revealed that, despite lacking 39% of its effector repertoire, infection with CRM12 results in similar changes to global protein expression as seen in mice infected with the wild-type strain, though key regulators of barrier integrity were differentially expressed. Using a host with impaired barrier repair (Il22− /− mice), we confirmed that accessory effectors collectively shape infection outcomes without significantly impacting virulence. This study refines the concept of core and accessory effectors, providing a basis for further studies into effector-driven host adaptation.
Date Issued
2025-12-31
Date Acceptance
2025-06-23
Citation
Gut Microbes, 2025, 17 (1)
ISSN
1949-0976
Publisher
Taylor & Francis Group
Journal / Book Title
Gut Microbes
Volume
17
Issue
1
Copyright Statement
© 2025 The Author(s). Published with license by Taylor & Francis Group, LLC. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40599135
Subjects
<italic>Citrobacter rodentium</italic>
barrier disruption
CELLS
CITROBACTER-RODENTIUM
ENTEROPATHOGENIC ESCHERICHIA-COLI
Gastroenterology & Hepatology
gut infection
IL-22
IMMUNITY
Life Sciences & Biomedicine
MAINTENANCE
MICE
Microbiology
mucosal immune responses
PATHOGEN
PATHOLOGY
Science & Technology
Type III secretion system effectors
Publication Status
Published
Coverage Spatial
United States
Article Number
2526134
Date Publish Online
2025-07-02