The mammalian neuroendocrine hormone norepinephrine supplies iron for bacterial growth in the presence of transferrin or lactoferrin

Norepinephrine stimulates the growth of a range of bacterial species in nut ritionally poor SAPI minimal salts medium containing 30% serum. Addition of size-fractionated serum components to SAPI medium indicated that transferr in was required for norepinephrine stimulation of growth of Escherichia col i, Since bacteriostasis by serum is primarily due to the iron-withholding c apacity of transferrin, we considered the possibility that norepinephrine c an overcome this effect by supplying transferrin-bound iron for growth, Inc ubation with concentrations of norepinephrine that stimulated bacterial gro wth in serum-SAPI medium resulted in loss of bound iron from iron-saturated transferrin, as indicated by the appearance of monoferric and apo-isoforms upon electrophoresis in denaturing gels. Norepinephrine also caused the lo ss of iron from lactoferrin. The pharmacologically inactive metabolite nore pinephrine 3-O-sulfate, by contrast, did not result in iron loss from trans ferrin or lactoferrin and did not stimulate bacterial growth in serum-SAPI medium. Norepinephrine formed stable complexes with transferrin, lactoferri n, and serum albumin. Norepinephrine-transferrin and norepinephrine-lactofe rrin complexes, but not norepinephrine-apotransferrin or norepinephrine-alb umin complexes, stimulated bacterial growth in serum-SAPI medium in the abs ence of additional norepinephrine. Norepinephrine-stimulated growth in medi um containing Fe-55 complexed with transferrin or lactoferrin resulted in u ptake of radioactivity by bacterial cells. Moreover, norepinephrine-stimula ted growth in medium containing [H-3] norepinephrine indicated concomitant uptake of norepinephrine. In each case, addition of excess iron did not aff ect growth but significantly reduced levels of radioactivity (Fe-55 or H-3) associated with bacterial cells. A role for catecholamine-mediated iron su pply in the pathophysicology of infectious diseases is proposed.