Glutathione is a target in tellurite toxicity and is protected by tellurite resistance determinants in Escherichia coli

Tellurite (TeO32-) is highly toxic to most microorganisms. The mechanisms o f toxicity or resistance are poorly understood. It has been shown that tell urite rapidly depletes the reduced thiol content within wild-type Escherich ia coli. We have shown that the presence of plasmid-borne tellurite-resista nce determinants protects against general thiol oxidation by tellurite. In the present study we observe that the tellurite-dependent depletion of cell ular thiols in mutants of the glutathione and thioredoxin thiol:redox syste m was less than in wild-type cells. To identify the type of low-molecular-w eight thiol compounds affected by tellurite exposure, the thiol-containing molecules were analyzed by reverse phase HPLC as their monobromobimane deri vatives. Results indicated that reduced glutathione is a major initial targ et of tellurite reactivity within the cell. Other thiol species are also ta rgeted by tellurite, including reduced coenzyme A. The presence of the tell urite resistance determinants kilA and ter protect against the loss of redu ced glutathione by as much as 60% over a 2 h exposure. This protection of g lutathione oxidation is likely key to the resistance mechanism of these det erminants. Additionally, the thiol oxidation response curves were compared between selenite and tellurite. The loss of thiol compounds within the cell recovered from selenite but not to tellurite.