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Updated: Jan 10, 2026
Chronic Salmonella Infection Induced Intestinal Fibrosis
Published on: September 22, 2019
Persistence mechanisms of Crohn's disease-associated adherent invasive Escherichia coli within macrophages
Emma Bruder1, Hosni Nedjar1, Nicole Quenech'Du1
1CIRB - Collège de France, CNRS, INSERM, Université PSL, Paris, France.
Abstract:
Patients with Crohn's disease exhibit abnormal intestinal colonization by Proteobacteria, particularly adherent-invasive Escherichia coli (AIEC). These bacteria predominate in the mucus, adhere to epithelial cells, colonize them, and survive inside macrophages. We recently demonstrated that the AIEC strain LF82 adapts to phagolysosomal stress through a two-step process: initial replication arrest generating stress-tolerant persisters, followed by the resumption of replication, leading to the formation of intracellular bacterial communities (IBCs) embedded in a biofilm-like matrix. Given the significant genomic diversity among strains with the AIEC phenotype, we performed a comparative genomic and functional analysis of 13 AIEC isolates from Crohn's disease patients in France and Spain. Our results demonstrate that IBCs are replicative niches for all AIEC strains within THP-1 macrophages, yet their formation relies on distinct mechanisms, including variations in phagosome detoxification, biofilm architecture, and macrophage responses. Our study identifies a strong positive correlation between vacuole acidification and persister induction, which underlies the intracellular survival of the different strains. Furthermore, we revealed distinct AIEC dissemination strategies outside macrophages, potentially contributing to the propagation of inflammation in the human host. These findings highlight that research on pathogens and pathobionts with dynamic genomes should extend beyond classical bacterial models.
Insights
Adherent-invasive Escherichia coli (AIEC) strains from Crohn's disease patients form distinct intracellular communities within macrophages. These bacteria utilize varied mechanisms for survival and dissemination, impacting host inflammation.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Crohn's disease is associated with abnormal gut microbiota, including Proteobacteria.
- Adherent-invasive Escherichia coli (AIEC) are key pathobionts implicated in Crohn's disease pathogenesis.
- AIEC colonize epithelial cells, survive within macrophages, and form intracellular bacterial communities (IBCs).
Purpose of the Study:
- To investigate the genomic diversity and functional mechanisms of AIEC strains isolated from Crohn's disease patients.
- To compare the formation and characteristics of IBCs among different AIEC strains.
- To elucidate AIEC adaptation strategies, including persister formation and dissemination.
Main Methods:
- Comparative genomic analysis of 13 AIEC isolates from Crohn's disease patients.
- Functional assays using THP-1 macrophages to study intracellular survival and IBC formation.
- Analysis of bacterial adaptation to phagolysosomal stress and persister induction.
- Investigation of AIEC dissemination strategies outside host cells.
Main Results:
- All tested AIEC strains formed replicative IBCs within macrophages, but via distinct mechanisms.
- Variations in phagosome detoxification, biofilm structure, and host cell responses influenced IBC formation.
- A positive correlation was observed between vacuole acidification and persister cell induction.
- Distinct AIEC dissemination strategies were identified, potentially contributing to inflammation.
Conclusions:
- AIEC strains exhibit significant functional diversity in their interaction with host macrophages.
- Phagolysosomal stress adaptation, particularly persister formation, is crucial for AIEC intracellular survival.
- Understanding AIEC pathoadaptation is essential for developing targeted therapies for Crohn's disease.
- Research should consider the dynamic nature of pathobiont genomes beyond classical models.
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