Arsenate reduction mediated by the plasmid-encoded ArsC protein is coupled to glutathione.
Resistance to arsenate conferred on Escherichia coli by the ars operon of plasmid R773 requires both the product of the arsC gene and reduction of arsenate to arsenite. A genetic analysis was performed to identify the source of reducing potential in vivo. In addition to the ars genes, arsenate resistance required the products of the gor gene for glutathione reductase and the gshA and gshB genes for glutathione synthesis. Mutations in the trx and grx genes for thioredoxin and glutaredoxin, respectively, had no effect on arsenate resistance. Although resistance required the arsC gene, the rate of reduction of arsenate to arsenite was nearly the same in cells lacking the ars operon. In strains deficient in glutathione biosynthesis this endogenous reduction was greatly diminished, and cells exhibited increased sensitivity to arsenate. When glutathione was supplied exogenously to such mutants, resistance was restored only to cells expressing the ars operon, and only such cells had detectable arsenate reduction after addition of glutathione. Since ArsC-catalysed reduction of arsenate provides high level resistance, physical coupling of the ArsC reaction to efflux of the resulting arsenite is hypothesised.
Oden
K L
KL
Department of Biochemistry, School of Medicine, Wayne State University, Detroit, Michigan 48201.
Gladysheva
T B
TB
Rosen
B P
BP
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D001149:Arsenates / Q000378:metabolism* / Q000494:pharmacology; D053501:Arsenite Transporting ATPases; D018053:Arsenites / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004352:Drug Resistance, Microbial / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D015870:Gene Expression; D054477:Glutaredoxins; D005978:Glutathione / Q000378:metabolism* / Q000494:pharmacology; D016623:Ion Pumps; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009097:Multienzyme Complexes; D009876:Operon; D010084:Oxidation-Reduction; D010088:Oxidoreductases; D010957:Plasmids / Q000235:genetics*; D011506:Proteins / Q000502:physiology; D017384:Sequence Deletion; D013879:Thioredoxins / Q000378:metabolism
D001149:Arsenates; D018053:Arsenites; D001426:Bacterial Proteins; D054477:Glutaredoxins; D016623:Ion Pumps; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D011506:Proteins; D013879:Thioredoxins; D010088:Oxidoreductases; D000251:Adenosine Triphosphatases; D053501:Arsenite Transporting ATPases; D005978:Glutathione; C015001:arsenite; C025657:arsenic acid