The assembly of a hybrid type IV secretion system by a Crohn’s disease associated Escherichia coli strain
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Published version
Author(s)
Type
Journal Article
Abstract
Type IV secretion systems (T4SSs) are central to bacterial pathogenesis. Traditionally known for facilitating DNA transfer via conjugation, T4SSs also mediate biofilm formation. These biofilms are critical for the fitness of adherent-invasive Escherichia coli (AIEC), which are commonly isolated from Crohn’s disease patients and are known for propelling gut inflammation. Many AIEC strains carry F-like plasmids encoding the IncF subgroup of T4SSs. Unlike minimized systems with 12 core components, the IncF family is an expanded T4SS with additional genes that enhance conjugation. Here, we show that a biofilm-forming AIEC strain harbors an unusual IncF plasmid that lacks two conserved components essential for T4SS functionality. This strain forms a natural hybrid T4SS where the missing components are supplied by a co-residing chromosomal T4SS on an integrative and conjugative element (ICE). Biochemical assays reveal that this hybrid T4SS drives pilin polymerization and biofilm formation on epithelial cells. Furthermore, we show that a bacterial subpopulation expresses the IncF and ICE-encoded genes in response to host cells, leading to the assembly of biofilms and enhanced fitness in the gut. These findings uncover crosstalk between two evolutionary distant mobile genetic elements to form a hybrid T4SS that mediates biofilm biogenesis by a Crohn’s disease-associated pathogen.
Date Issued
2025-10-02
Date Acceptance
2025-08-26
Citation
Nature Communications, 2025, 16
ISSN
2041-1723
Publisher
Nature Portfolio
Journal / Book Title
Nature Communications
Volume
16
Copyright Statement
© The Author(s) 2025 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Publication Status
Published
Article Number
8797
Date Publish Online
2025-10-02
