Transcriptomic Changes in Pathogenic E. coli Infection

Enteropathogenic Escherichia coli (EPEC) is a significant cause of childhood diarrheal disease, especially in developing countries, and is associated with high mortality rates in children under five years old. Despite decades of research into the pathogenesis of infection, a systemic view of what happens in the host and the pathogen at various stages of disease is still lacking. In this study, we employed a dual RNA-sequencing approach to investigate both the host and pathogen responses during EPEC infection of a human intestinal epithelial cell line (Caco-2/TC-7) with a focus on the role of the bacterial type III secretion virulence system (T3SS) in modulating host-pathogen interactions. Our findings show that host defenses dominated the transcriptional response early in infection, and the T3SS had a moderate impact in manipulating proinflammatory host signaling. We also observed significant changes in the bacterial transcriptome upon host-cell contact, including regulation of virulence genes and reprogramming of metabolic pathways During a prolonged infection using polarized TC-7 cells, EPEC utilized its T3SS to suppress essential host responses, including immune signaling and apoptosis. Furthermore, we identified differentially expressed miRNAs that play a role in inhibiting death and altering cytokine secretion in response to infection. These results provide the first overview of the transcriptomic changes in the host cells at various stages of EPEC infection, and identify several miRNAs that are vital for modulating infection outcome.