Bacteria communicate with host cells through signaling molecules, a process known as quorum sensing (QS). Enterohemorrhagic Escherichia coli (EHEC) uses QS to sense its environment and activate genes essential for intestinal colonization. The QS system in EHEC involves the LuxS/autoinducer 2 (AI-2) system, which is involved in interspecies communication. However, EHEC also uses another autoinducer, AI-3, which is synthesized in the presence of LuxS. This study shows that EHEC responds to the eukaryotic hormone epinephrine (Epi) to activate its virulence genes. The response to Epi is blocked by β- and α-adrenergic antagonists, suggesting a cross-communication between the LuxS/AI-3 bacterial QS system and the Epi host signaling system. The results imply that QS might be a "language" by which bacteria and host cells communicate. EHEC produces Shiga toxin, which is responsible for the major symptoms of hemorrhagic colitis and hemolytic uremic syndrome (HUS). The LEE pathogenicity island, which contains genes for the type III secretion system, adhesin, and receptor, is essential for EHEC colonization. QS activates the LEE genes, which are involved in the formation of attaching and effacing (AE) lesions on intestinal epithelial cells. The study also shows that AI-2 is not the autoinducer involved in the bacterial signaling, as in vitro-synthesized AI-2 does not activate LEE gene transcription. Instead, AI-3, which is produced by the intestinal flora, is the actual signal activating transcription of the LEE and flagella genes. The results suggest that AI-3 and Epi may signal through the same pathway, and that AI-3 may be a novel compound also inhibited by adrenergic antagonists. The study also shows that Epi can substitute for AI-3 to activate transcription of the LEE genes, type III secretion, and AE lesions on HeLa cells. These findings suggest that QS may be a language by which bacteria and host cells communicate, either through an amicable or detrimental interaction. The study highlights the importance of understanding bacterial-host communication in the context of pathogenesis and symbiosis.Bacteria communicate with host cells through signaling molecules, a process known as quorum sensing (QS). Enterohemorrhagic Escherichia coli (EHEC) uses QS to sense its environment and activate genes essential for intestinal colonization. The QS system in EHEC involves the LuxS/autoinducer 2 (AI-2) system, which is involved in interspecies communication. However, EHEC also uses another autoinducer, AI-3, which is synthesized in the presence of LuxS. This study shows that EHEC responds to the eukaryotic hormone epinephrine (Epi) to activate its virulence genes. The response to Epi is blocked by β- and α-adrenergic antagonists, suggesting a cross-communication between the LuxS/AI-3 bacterial QS system and the Epi host signaling system. The results imply that QS might be a "language" by which bacteria and host cells communicate. EHEC produces Shiga toxin, which is responsible for the major symptoms of hemorrhagic colitis and hemolytic uremic syndrome (HUS). The LEE pathogenicity island, which contains genes for the type III secretion system, adhesin, and receptor, is essential for EHEC colonization. QS activates the LEE genes, which are involved in the formation of attaching and effacing (AE) lesions on intestinal epithelial cells. The study also shows that AI-2 is not the autoinducer involved in the bacterial signaling, as in vitro-synthesized AI-2 does not activate LEE gene transcription. Instead, AI-3, which is produced by the intestinal flora, is the actual signal activating transcription of the LEE and flagella genes. The results suggest that AI-3 and Epi may signal through the same pathway, and that AI-3 may be a novel compound also inhibited by adrenergic antagonists. The study also shows that Epi can substitute for AI-3 to activate transcription of the LEE genes, type III secretion, and AE lesions on HeLa cells. These findings suggest that QS may be a language by which bacteria and host cells communicate, either through an amicable or detrimental interaction. The study highlights the importance of understanding bacterial-host communication in the context of pathogenesis and symbiosis.