Title: Persistence mechanisms of Crohn’s disease-associated adherent-invasive Escherichia coli within macrophages | Gut Microbes
Background
Patients with Crohn’s disease (CD) often carry mucosa-adherent AIEC strains that can evade antibiotics and drive chronic inflammation. But how genetically different AIEC isolates manage to survive long-term inside macrophages hasn’t been clear.
Methods
A collaborative team from France and Spain collected 13 clinical AIEC isolates, infected THP-1 macrophages, and tracked the bacteria’s intracellular fate using plating assays, live-cell imaging, vacuole pH ratiometry, and comparative genomics. They also used RNA-seq to capture transcriptional signatures during both the replication-arrest and regrowth phases.
Key findings
All tested strains formed biofilm-embedded intracellular bacterial communities (IBCs) inside macrophages. Notably, the intensity of vacuole acidification correlated positively with persister levels (ρ = 0.83), which explained the strain-to-strain differences in survival. Genome-wide screening further linked diverse alleles of hya, yghJ, and pga to phagosome detoxification and non-lytic dissemination routes – mechanisms that may help seed new granulomas.
Implications
This work argues that we shouldn’t rely solely on the lab reference strain LF82 as a model. Instead, personalized anti-persister strategies tailored to different AIEC strains are needed.
Acknowledgement
RNA-sequencing services for this study were provided by BMKGENE.
Post time: Apr-14-2026
