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Journal of Bacteriology, August 2008, p. 5439-5454, Vol. 190, No. 15
0021-9193/08/$08.00+0     doi:10.1128/JB.00272-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Cadmium Toxicity in Glutathione Mutants of Escherichia coli ^,

Kerstin Helbig, Cornelia Grosse, and Dietrich H. Nies^*

Institute for Biology, Life Science Faculty, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 3, 06099 Halle, Germany

Received 22 February 2008/ Accepted 27 May 2008

The higher affinity of Cd²⁺ for sulfur compounds than for nitrogen and oxygen led to the theoretical consideration that cadmium toxicity should result mainly from the binding of Cd²⁺ to sulfide, thiol groups, and sulfur-rich complex compounds rather than from Cd²⁺ replacement of transition-metal cations from nitrogen- or oxygen-rich biological compounds. This hypothesis was tested by using Escherichia coli for a global transcriptome analysis of cells synthesizing glutathione (GSH; wild type), -glutamylcysteine (gshB mutant), or neither of the two cellular thiols (gshA mutant). The resulting data, some of which were validated by quantitative reverse transcription-PCR, were sorted using the KEGG (Kyoto Encyclopedia of Genes and Genomes) orthology system, which groups genes hierarchically with respect to the cellular functions of their respective products. The main difference among the three strains concerned tryptophan biosynthesis, which was up-regulated in wild-type cells upon cadmium shock and strongly up-regulated in gshA cells but repressed in gshB cells containing -glutamylcysteine instead of GSH. Overall, however, all three E. coli strains responded to cadmium shock similarly, with the up-regulation of genes involved in protein, disulfide bond, and oxidative damage repair; cysteine and iron-sulfur cluster biosynthesis; the production of proteins containing sensitive iron-sulfur clusters; the storage of iron; and the detoxification of Cd²⁺ by efflux. General energy conservation pathways and iron uptake were down-regulated. These findings indicated that the toxic action of Cd²⁺ indeed results from the binding of the metal cation to sulfur, lending support to the hypothesis tested.

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* Corresponding author. Mailing address: Institute for Biology, Life Science Faculty, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 3, 06099 Halle, Germany. Phone: (49) 345-5526352. Fax: (49) 345-5527010. E-mail: d.nies{at}mikrobiologie.uni-halle.de

Published ahead of print on 6 June 2008.

Supplemental material for this article may be found at http://jb.asm.org/.

These authors contributed equally to this study.

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Journal of Bacteriology, August 2008, p. 5439-5454, Vol. 190, No. 15
0021-9193/08/$08.00+0     doi:10.1128/JB.00272-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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