47 / 2026-03-30 14:57:15

Elucidating the genomic interaction mechanisms between bacteriophage T7 and Escherichia coli BL21 based on chromosome conformation capture

3D genome,Escherichia coli BL21,Bacteriophage T7,Bacteriophage–host interaction

Chromatin conformation capture technologies have revealed that prokaryotic genomes adopt highly organized three-dimensional (3D) architectures; however, how viral and host genomes spatially interact during bacteriophage infection remains unclear. Here, using T7 phage infection of Escherichia coli BL21 as an experimental subject, we integrate Hi-C, transcriptomic and DNA methylation analyses to characterize the spatiotemporal reprogramming of the host nucleoid.

We show that upon infection, T7 DNA rapidly forms head-to-tail concatemer that dominate the intracellular 3D landscape, while the host chromosome becomes more compact with enhanced local interactions. The phage genome preferentially associates with host regions enriched in membrane, metabolic and ribosomal genes, suggesting spatial targeting of resource-rich domains. Concomitantly, the host genome reorganizes into distinct chromatin interaction domains enriched for metabolic regulation and DNA repair functions.

Transcriptomic profiling reveals temporally ordered phage gene expression and global suppression of host transcription, with early stress responses followed by metabolic reprogramming and a reduced late-stage transcriptional state. These transcriptional dynamics are closely coupled to 3D genome reorganization, indicating coordinated spatial and functional regulation. In contrast to relatively stable host DNA methylation, phage DNA exhibits stage-specific methylation changes, with differentially methylated regions enriched in regulatory elements, potentially modulating DNA–protein interactions.

Together, our results suggest that T7 phage establishes a peripheral replication center and exploits host 3D genome organization by positioning its genome within transcriptionally active regions, thereby facilitating efficient resource acquisition and gene expression. This study uncovers a spatially coordinated mechanism of phage–host interaction at the level of 3D genome organization.