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Journal of Bacteriology, November 2000, p. 6091-6098, Vol. 182, No. 21
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

The Mammalian Neuroendocrine Hormone Norepinephrine Supplies Iron for Bacterial Growth in the Presence of Transferrin or Lactoferrin

Primrose P. E. Freestone,1 Mark Lyte,2 Christopher P. Neal,1 Anthony F. Maggs,1,dagger Richard D. Haigh,1 and Peter H. Williams1,*

Department of Microbiology & Immunology, University of Leicester, Leicester LE1 9HN, United Kingdom,1 and Minneapolis Medical Research Foundation, Hennepin County Medical Center, Minneapolis, Minnesota 554042

Received 15 June 2000/Accepted 8 August 2000

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 55Fe complexed with transferrin or lactoferrin resulted in uptake of radioactivity by bacterial cells. Moreover, norepinephrine-stimulated growth in medium containing [3H]norepinephrine indicated concomitant uptake of norepinephrine. In each case, addition of excess iron did not affect growth but significantly reduced levels of radioactivity (55Fe or 3H) associated with bacterial cells. A role for catecholamine-mediated iron supply in the pathophysiology of infectious diseases is proposed.

* Corresponding author. Mailing address: University of Leicester, Department of Microbiology & Immunology, Medical Sciences Building, University Road, Leicester LE1 9HN, United Kingdom. Phone: 44 116 252 3436. Fax: 44 116 252 5030. E-mail: phw2{at}le.ac.uk.

dagger Present address: Department of Microbiology, Torbay Hospital, Torquay, Devon GQ2 7AA, United Kingdom.

Journal of Bacteriology, November 2000, p. 6091-6098, Vol. 182, No. 21
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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