Blockade of catecholamine-induced growth by adrenergic and dopaminergic receptor antagonists in Escherichia coli O157:H7, Salmonella enterica and Yersinia enterocolitica

Abstract

Background: The ability of catecholamines to stimulate bacterial growth was first demonstrated just over a decade ago. Little is still known however, concerning the nature of the putative bacterial adrenergic and/or dopaminergic receptor(s) to which catecholamines (norepinephrine, epinephrine and dopamine) may bind and exert their effects, or even whether the binding properties of such a receptor are similar between different species.

Results: Use of specific catecholamine receptor antagonists revealed that only alpha, and not beta, adrenergic antagonists were capable of blocking norepinephrine and epinephrine-induced growth, while antagonism of dopamine-mediated growth was achieved with the use of a dopaminergic antagonist. Both adrenergic and dopaminergic antagonists were highly specific in their mechanism of action, which did not involve blockade of catecholamine-facilitated iron-acquisition. Use of radiolabeled norepinephrine suggested that the adrenergic antagonists could be acting by inhibiting catecholamine uptake.

Conclusion: The present data demonstrates that the ability of a specific pathogen to respond to a particular hormone is dependent upon the host anatomical region in which the pathogen causes disease as well as the neuroanatomical specificity to which production of the particular hormone is restricted; and that both are anatomically coincidental to each other. As such, the present report suggests that pathogens with a high degree of exclusivity to the gastrointestinal tract have evolved response systems to neuroendocrine hormones such as norepinephrine and dopamine, but not epinephrine, which are found with the enteric nervous system.

Figure 1

α-Adrenergic antagonist inhibition of bacterial uptake of NE. Washed exponential cultures of E. coli O157:H7, S. enterica, or Y. enterocolitica were added at a cell density of around 2 × 10⁸ CFU/ml to DMEM containing 50 μM NE plus 5 × 10⁵ cpm/ml of ³H-NE and the following: no additions (Control), or 200 μM phentolamine, phenoxybenzamine or prazosin. Cultures were incubated statically for 6 hrs at 37°C in a 5% CO₂ humidified incubator, and analysed for growth and ³H-NE uptake as described in Materials and Methods. ³H-NE uptake assays were performed in duplicate on at least two occasions; variation within individual assay sets was 5% or less, and between experiments no more than 10%. Antagonist supplemented cultures showed statistically significant decreases in uptake of ³H-NE (P < 0.001) as compared with the Control.