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Here, we found that EPEC induced isolated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    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 Ca\n                    <jats:sup>2+<\/jats:sup>\n                    imaging, we uncovered that at the onset of infection, low eATP levels triggered Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -responses involving the whole cell but showing small amplitude and fast kinetics usually associated with local Ca\n                    <jats:sup>2+<\/jats:sup>\n                    responses. The findings, supported by theoretical modeling, evoke a conceptual shift whereby low amounts of inositol 1, 4, 5-trisphosphate (IP\n                    <jats:sub>3<\/jats:sub>\n                    ) induced by low eATP levels and subsequent moderate Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release enable the fast coordination of IP\n                    <jats:sub>3<\/jats:sub>\n                    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 Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -dependent O-linked \u03b2-\n                    <jats:italic>N<\/jats:italic>\n                    -acetylglucosamine modification.\n                  <\/jats:p>","DOI":"10.7554\/elife.108953","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T14:30:48Z","timestamp":1766500248000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.108953","source":"Crossref","is-referenced-by-count":0,"title":["Enteropathogenic Escherichia coli-mediated fast and coordinated Ca\u00b2+ responses regulate NF-\u03baB activation"],"prefix":"10.7554","volume":"14","author":[{"given":"Fangrui","family":"Guo","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03xjwb503","id-type":"ROR","asserted-by":"publisher"}],"name":"Team 'Ca\u00b2\u207a signaling and Microbial Infections,' Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS UMR9198, Universit\u00e9 Paris-Saclay","place":["Gif-sur-Yvette, France"]},{"id":[{"id":"https:\/\/ror.org\/02vjkv261","id-type":"ROR","asserted-by":"publisher"}],"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","place":["Gif-sur-Yvette, France"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Roberto","family":"Ornelas 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