Enteropathogenic Escherichia coli-mediated fast and coordinated Ca^²+ responses regulate NF-κB activation.

Authors

Fangrui Guo, Roberto Ornelas Guevara, Linda Oussaedine, Geneviève Dupont, Laurent Combettes, Guy Tran Van Nhieu

Published in

eLife. Volume 14. Jul 22, 2026. Epub Jul 22, 2026.

Abstract

Enteropathogenic Escherichia coli (EPEC) is a major bacterial enteropathogen causing infectious diarrhea among children in developing countries. Here, we found that EPEC induced isolated Ca²⁺ responses in epithelial cells, triggered by extracellular ATP (eATP). These responses were dependent on type III secretion (T3S) and down-regulated by the bacterial secreted protease EspC, consistent with eATP released by the T3S translocon pore-forming activity in host membranes. By performing high-speed Ca²⁺ imaging, we uncovered that at the onset of infection, low eATP levels triggered Ca²⁺-responses involving the whole cell but showing small amplitude and fast kinetics usually associated with local Ca²⁺ responses. The findings, supported by theoretical modeling, evoke a conceptual shift whereby low amounts of inositol 1, 4, 5-trisphosphate (IP₃) induced by low eATP levels and subsequent moderate Ca²⁺ release enable the fast coordination of IP₃ receptor cluster activation throughout the cell. Importantly, these yet undescribed coordinated fast responses occurred over prolonged time periods and defined a cell state with dampened activation of the pro-inflammatory transcriptional activator NF-kB associated with a decrease in its Ca²⁺-dependent O-linked β-N-acetylglucosamine modification.

PMID:
42484621
Bibliographic data and abstract were imported from PubMed on 22 Jul 2026.

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