Tellurite exerts a deleterious effect on a number of small molecules containing sulfur moieties that have a recognized role in cellular oxidative stress. Because cysteine is involved in the biosynthesis of glutathione and other sulfur-containing compounds, we investigated the expression of Geobacillus stearothermophilus V cysteinerelated genes cobA, cysK, and iscS and Escherichia coli cysteine regulon genes under conditions that included the addition of K 2 TeO 3 to the culture medium. Results showed that cell tolerance to tellurite correlates with the expression level of the cysteine metabolic genes and that these genes are up-regulated when tellurite is present in the growth medium.Sulfur is an essential element that is required for the biosynthesis of proteins, enzyme cofactors, and other important biomolecules. In bacteria, this element can be assimilated into sulfur-containing amino acids through enzymatic fixation from inorganic sources, such as sulfate and/or thiosulfate (15, 38). Although tellurium shares several chemical properties with sulfur, no biological function for Te is known to date. Conversely, some tellurium compounds, like the oxyanion tellurite (TeO 3 2Ϫ ), are extremely toxic for most forms of life, especially microorganisms (34).It has been proposed that K 2 TeO 3 toxicity could be due to the oxidation of cellular thiols such as glutathione (37) or the generation of superoxide radical during tellurite reduction, which would cause a redox imbalance resulting in intracellular oxidative stress (5,23,26,33,34,36).Maintenance of cell redox balance is one of the most important processes involving molecules synthesized from reduced sulfur taken from the environment. Glutathione (GSH) is one of the major nonprotein thiols in living organisms, including humans, yeast, and bacteria (6, 10). GSH has been involved in resistance to osmotic and oxidative stress as well as in Escherichia coli resistance to the toxic effects of electrophiles like methylglyoxal (6,11,31). A protective effect of GSH against oxidative stress has also been described for Lactococcus lactis and Rhodobacter capsulatus (17,18).Three genes involved in tellurite resistance have been described previously for the thermotolerant gram-positive rod Geobacillus stearothermophilus V (27, 33, 41). The genes that are involved in the metabolism of cysteine are cysK, iscS, and cobA, and they encode a cysteine synthase (CysK), a cysteine desulfurase (IscS), and a uroporphyrinogen-III C-methyltransferase (SUMT), respectively. CysK catalyzes the last step of inorganic sulfur fixation into L-cysteine, while SUMT is involved in the biosynthesis of siroheme, an essential sulfite reductase cofactor that participates in the inorganic assimilation of sulfur (15). We recently demonstrated that cobA and ubiE genes from G. stearothermophilus V confer increased tolerance to oxyanions of selenium and tellurium when expressed in E. coli (1, 32). Finally, IscS, which yields sulfur and L-alanine from L-cysteine, has been shown to be involved, along with IscA ...