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Journal of Bacteriology, August 1999, p. 4774-4779, Vol. 181, No. 16
Department of Biochemistry and Biophysics,
University of Rochester School of Medicine and Dentistry,
Rochester, New York 14642
Received 1 April 1999/Accepted 3 June 1999
The pH-dependent inhibition of 22 metal salts have been
systematically investigated for the yeast Saccharomyces
cerevisiae. We have established that the inhibition of growth by
Cu, Co, or Ni salts is markedly enhanced by histidine auxotrophy and by
increasing the pH of the medium. Each of the his1-his7
mutant strains were unable to grow in the presence of elevated levels
of Cu, Co, or Ni at nearly neutral pHs, in contrast to His+
strains, which grew under these conditions. The Cu, Co, or Ni inhibition was reversed by the addition of histidine to the medium. Deletion of the high-affinity histidine permease Hip1p in
His
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Toxicity of Copper, Cobalt, and Nickel Salts Is
Dependent on Histidine Metabolism in the Yeast
Saccharomyces cerevisiae
strains resulted in even greater sensitivity to Cu,
Co, and Ni and the requirement of an even higher level of histidine to
reverse the inhibition. These results suggest that intracellular
histidine, most likely in the vacuole, diminishes the pH-dependent
toxicity of Cu, Co, and Ni. Furthermore, the toxicity of many salts is exacerbated in strains with a defective vacuolar H+-ATPase,
which abolishes the ability of yeast to maintain an acidic vacuole, a
compartment known to sequester metal compounds. We suggest that the
accumulation of histidine in the vacuole is a normal process used to
detoxify Cu, Co, and Ni.
*
Corresponding author. Mailing address: Department of
Biochemistry and Biophysics, Box 712, University of Rochester School of
Medicine and Dentistry, Rochester, NY 14642. Phone: (716) 275-6647. Fax: (716) 271-2683. E-mail:
Fred_Sherman{at}urmc.rochester.edu.
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