Positive control of a global antioxidant defense regulon activated by superoxide-generating agents in Escherichia coli.
Escherichia coli responds to superoxide-generating agents by inducing approximately 40 proteins. We have identified a genetic locus, soxR (superoxide response), that positively regulates 9 of these proteins during superoxide stress. Induction under soxR control is at the transcriptional level, as shown with lac fusions to five paraquat-inducible promoters. Members of the soxR regulon include at least three proteins with demonstrable antioxidant roles: Mn-containing superoxide dismutase (which destroys superoxide radicals), endonuclease IV (which repairs radical-induced damages in DNA), and glucose-6-phosphate dehydrogenase (which produces NADPH). Induction of the soxR regulon also leads to diminished levels of the major outer membrane protein OmpF and alteration of the small-subunit ribosomal protein S6. These latter changes confer resistance to a variety of antibiotics. The soxR regulon may thus operate as an inducible defense against xenobiotics in general.
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.
J T
JT
Greenberg
P
P
Monach
J H
JH
Chou
P D
PD
Josephy
B
B
Demple
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D004251:DNA Transposable Elements; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D043223:Deoxyribonuclease IV (Phage T4-Induced); D004352:Drug Resistance, Microbial / Q000235:genetics; D004706:Endodeoxyribonucleases / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics*; D029968:Escherichia coli Proteins; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D005809:Genes, Regulator; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics*; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D009876:Operon; D011815:R Factors; D013482:Superoxide Dismutase / Q000235:genetics*; D013481:Superoxides / Q000378:metabolism / Q000494:pharmacology*; D014161:Transduction, Genetic
D000900:Anti-Bacterial Agents; D000975:Antioxidants; D004251:DNA Transposable Elements; D029968:Escherichia coli Proteins; D013481:Superoxides; D008769:Methylnitronitrosoguanidine; D005954:Glucosephosphate Dehydrogenase; D013482:Superoxide Dismutase; D004706:Endodeoxyribonucleases; D043223:Deoxyribonuclease IV (Phage T4-Induced); C468972:endonuclease IV, E coli; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase