title: Glutathione is a target in tellurite toxicity and is protected by tellurite resistance determinants in Escherichia coli.
abstract: Tellurite (TeO3(2-)) is highly toxic to most microorganisms. The mechanisms of toxicity or resistance are poorly understood. It has been shown that tellurite rapidly depletes the reduced thiol content within wild-type Escherichia coli. We have shown that the presence of plasmid-borne tellurite-resistance determinants protects against general thiol oxidation by tellurite. In the present study we observe that the tellurite-dependent depletion of cellular thiols in mutants of the glutathione and thioredoxin thiol:redox system was less than in wild-type cells. To identify the type of low-molecular-weight thiol compounds affected by tellurite exposure, the thiol-containing molecules were analyzed by reverse phase HPLC as their monobromobimane derivatives. Results indicated that reduced glutathione is a major initial target of tellurite reactivity within the cell. Other thiol species are also targeted by tellurite, including reduced coenzyme A. The presence of the tellurite resistance determinants kilA and ter protect against the loss of reduced glutathione by as much as 60% over a 2 h exposure. This protection of glutathione oxidation is likely key to the resistance mechanism of these determinants. 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.
authors.affiliation: Structural Biology Research Group, Department Biological Sciences, University of Calgary, Calgary, AB T2N 1N4, Canada. turnerr@ucalgary.ca
authors.forename: R J
authors.initials: RJ
authors.lastname: Turner
authors.forename: Y
authors.initials: Y
authors.lastname: Aharonowitz
authors.forename: J H
authors.initials: JH
authors.lastname: Weiner
authors.forename: D E
authors.initials: DE
authors.lastname: Taylor
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D003065:Coenzyme A; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000502:physiology; D005978:Glutathione / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010084:Oxidation-Reduction; D010957:Plasmids / Q000235:genetics; D018038:Sodium Selenite / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism; D013691:Tellurium / Q000633:toxicity*; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D013438:Sulfhydryl Compounds; C067119:kilA protein, E coli; D013879:Thioredoxins; D005978:Glutathione; D018038:Sodium Selenite; C026660:tellurous acid; D013691:Tellurium; D003065:Coenzyme A