Differential Effects of Epinephrine and Norepinephrine on Bacterial Growth and Biofilm Formation in E. coli Strains and S. aureus

<title>Abstract</title> <p> <bold>Background</bold> Physiological stress activates the sympathetic nervous system, triggering systemic release of catecholamines such as epinephrine and norepinephrine. Beyond their canonical roles in host physiology, these neuroendocrine hormones serve as interkingdom signaling molecules, directly modulating bacterial behavior. Accumulating evidence implicates catecholamines in regulating microbial growth, virulence, and biofilm formation. Yet, systematic comparative analyses of individual catecholamines on Gram-negative and Gram-positive pathogens under controlled conditions remain scarce. This study investigates the differential effects of epinephrine and norepinephrine on bacterial proliferation and biofilm formation in clinically relevant species. <bold>Methods</bold> Escherichia coli ATCC 25922, enterohemorrhagic E. coli O157:H7 ATCC 43895, and Staphylococcus aureus ATCC 25923 were exposed to physiologically relevant catecholamine concentrations (5, 10, 50, 100 µM) in vitro. Planktonic growth was quantified after 24 hours at 37°C via optical density at 600 nm (OD₆₀₀). Biofilm formation was assessed using a crystal violet microtiter assay measured at 570 nm (OD₅₇₀). Statistical significance was determined using one-way analysis of variance (ANOVA), at p &lt; 0.05. <bold>Results</bold> Catecholamines elicited robust, concentration-dependent, and species-specific responses. Both E. coli strains exhibited marked stimulation of growth and biofilm formation, with O157:H7 demonstrating the highest responsiveness. Norepinephrine preferentially enhanced planktonic proliferation, increasing growth by ~ 41%, whereas epinephrine exerted a dominant effect on biofilm formation, augmenting biomass by up to ~ 62%. In contrast, S. aureus displayed modest responses, with maximal growth and biofilm increases of ~ 11% and 19%, respectively. At the highest concentrations(100 µM), responses plateaued or slightly declined. <bold>Conclusion</bold> Host-derived catecholamines exert potent, species-specific regulation of bacterial growth dynamics and biofilm development. Gram-negative E. coli strains are particularly sensitive, underscoring the pivotal role of stress-associated neuroendocrine signaling in microbial adaptation and persistence. These insights advance our understanding of host–microbe interkingdom communication and may inform novel strategies to modulate pathogenicity by targeting catecholamine-mediated pathways. </p>