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 nutritionally poor SAPI minimal salts medium containing 30% serum. Addition of size-fractionated serum components to SAPI medium indicated that transferrin was required for norepinephrine stimulation of growth of Escherichia coli. Since bacteriostasis by serum is primarily due to the iron-withholding capacity of transferrin, we considered the possibility that norepinephrine can overcome this effect by supplying transferrin-bound iron for growth. Incubation with concentrations of norepinephrine that stimulated bacterial growth 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 loss of iron from lactoferrin. The pharmacologically inactive metabolite norepinephrine 3-O-sulfate, by contrast, did not result in iron loss from transferrin or lactoferrin and did not stimulate bacterial growth in serum-SAPI medium. Norepinephrine formed stable complexes with transferrin, lactoferrin, and serum albumin. Norepinephrine-transferrin and norepinephrine-lactoferrin complexes, but not norepinephrine-apotransferrin or norepinephrine-albumin complexes, stimulated bacterial growth in serum-SAPI medium in the absence of additional norepinephrine. Norepinephrine-stimulated growth in medium containing (55)Fe complexed with transferrin or lactoferrin resulted in uptake of radioactivity by bacterial cells. Moreover, norepinephrine-stimulated growth in medium containing [(3)H]norepinephrine indicated concomitant uptake of norepinephrine. In each case, addition of excess iron did not affect growth but significantly reduced levels of radioactivity ((55)Fe or (3)H) associated with bacterial cells. A role for catecholamine-mediated iron supply in the pathophysiology of infectious diseases is proposed.
Freestone
P P
PP
Department of Microbiology & Immunology, University of Leicester, Leicester LE1 9HN, United Kingdom.
Lyte
M
M
Neal
C P
CP
Maggs
A F
AF
Haigh
R D
RD
Williams
P H
PH
D000818:Animals; D003470:Culture Media; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development*; D006801:Humans; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D007504:Iron Radioisotopes; D007781:Lactoferrin / Q000378:metabolism*; D009638:Norepinephrine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D014168:Transferrin / Q000378:metabolism*; D014316:Tritium
D003470:Culture Media; D007504:Iron Radioisotopes; D014168:Transferrin; D014316:Tritium; C017574:noradrenaline sulfate; D007501:Iron; D007781:Lactoferrin; D009638:Norepinephrine