Disease relevance of oxyR

• Mutations in oxyR or rob, known regulators of several stress promoters in E. coli, had no effect on the induction of hmp by paraquat [1].
• The oxyR gene is required for the induction of a regulon of hydrogen peroxide-inducible genes in Escherichia coli and Salmonella typhimurium [2].
• To identify genes which might confer resistance by detoxifying or sequestering INH, we transformed the Escherichia coli oxyR mutant, which is relatively sensitive to INH, with a Mycobacterium tuberculosis plasmid library and selected for INH-resistant clones [3].
• The oxyR gene from the pathogenic bacterium Erwinia chrysanthemi has been characterized [4].
• CONCLUSIONS: The presented findings indicate major differences between M. tuberculosis and the paradigms of oxidative stress response in enteric bacteria, and are consistent with the multiple lesions found in oxyR of this organism [5].

High impact information on oxyR

• The oxyR gene positively regulates genes induced by oxidative stress in Salmonella typhimurium and Escherichia coli [6].
• Mutations that suppressed the H2O2 sensitivity of Escherichia coli oxyR- strains caused elevated levels of one three enzymes that destroy organic and hydrogen peroxides: catalase-hydroperoxidase I (the katG gene product), catalase-hydroperoxidase II (controlled by katEF) or alkyl hydroperoxide reductase (specified by the ahp genes) [7].
• The E. coli delta oxyR strains also exhibited a strongly elevated frequency of spontaneous mutagenesis, as reported for such mutants in Salmonella typhimurium [7].
• The continuous high-level expression of any one of these enzymes also conferred resistance in an oxyR deletion mutant against other compounds such as N-ethylmaleimide and the superoxide-generator menadione [7].
• One critical protein was Dps, an iron-sequestration protein, because Hpx- dps mutants exhibited sensitivity similar to that of the Hpx- oxyR mutant [8].

Chemical compound and disease context of oxyR

• To further define the mechanism by which oxyR regulates the production of these proteins, we identified, mapped, and characterized oxyR-regulated promoters upstream from the S. typhimurium ahp genes (encoding an alkyl hydroperoxide reductase) and the E. coli katG gene (encoding catalase) [9].
• The synthesis of manganese-superoxide dismutase in response to hydrogen peroxide and to paraquat was examined in strains of Escherichia coli with different mutations in the oxyR gene [10].
• Induction of the manganese-containing superoxide dismutase in Escherichia coli is independent of the oxidative stress (oxyR-controlled) regulon [10].
• Susceptibilities of oxyR regulon mutants of Escherichia coli and Salmonella typhimurium to isoniazid [11].
• The oxyR and oxyS genes of wild-type E. coli strain Ec1a (O1:K1:H7) were replaced with a kanamycin resistance cassette to produce an oxyRS mutant [12].

Biological context of oxyR

• An Hpx- oxyR strain exhibited even more DNA lesions than did the Hpx- mutant, indicating that the OxyR stress response induced protein(s) that suppressed DNA damage [8].
• The mor gene has been cloned and its DNA sequence determined [13].
• This gene has been designated mor and is located at 89 minutes on the E. coli chromosome map between the argECBH operon and the trmA gene [13].
• DNA sequence analysis of the oxyR2 mutation, which causes overexpression of oxyR-regulated proteins in the absence of oxidative stress, showed that the oxyR2 phenotype is due to a missense mutation (C.G to T.A transition) that changes alanine to valine at amino acid position 234 of OxyR [2].
• The E. coli oxyR gene has been cloned and sequenced, revealing an open reading frame (305 amino acids) that encodes a 34.4-kDa protein, which is produced in maxicells carrying the oxyR clone [2].

Anatomical context of oxyR

• Effect of inactivation of the global oxidative stress regulator oxyR on the colonization ability of Escherichia coli O1:K1:H7 in a mouse model of ascending urinary tract infection [12].
• Overexpression of the oxyR gene in mammalian tumor cell lines protects them from hydrogen peroxide-induced cell death, and these cells are also highly resistant to the superoxide ion producing compound paraquat [14].
• Our results suggest that the hypersensitivity observed in the oxyR mutants to the lethal effect of CHP does not appear to be due to SOS inducing DNA lesions, but rather to cell membrane damage [15].

Associations of oxyR with chemical compounds

• In stark contrast, the inactivation of both oxyR and rpoS genes dramatically decreased the viability of glucose-starved cells [16].
• The oxyR mutant was hypersusceptible to oxidative stress-generating agents, including H(2)O(2) and paraquat, in spite of total KatA catalase activity being comparable to that of the wild type [17].
• These results suggest that UV-A generates 1O2 or the hydroxyl radical to produce lipid peroxides intracellularly in the delta oxyR mutant and that O2- stress may be generated in the sodAB mutant after 8hr of exposure to UV-A [18].
• Catalase (HPI), but not manganese-superoxide dismutase, was over-expressed under anaerobic conditions in a strain harboring a constitutive oxyR mutation [10].
• Spermidine acetylation does not appear to be associated with known stress regulons, such as htpR, oxyR, and SOS [19].

Other interactions of oxyR

• Strains bearing mutations in oxyR and rpoH were the most hypersensitive to these compounds [20].
• Comparisons were made both by traditional and QPCR methods with similar results and indicate that the survival defect of an oxyR and oxyS mutant described previously can be attributed to the loss of oxyR alone [21].
• Mutants affected in recG but not oxyR were dramatically impaired in DNA damage repair as measured by sensitivity to UV irradiation [17].
• The peroxide-dependent topA P1 activation is independent of oxyR, but is mediated by Fis. This nucleoid-associated protein binds to the promoter region of topA [22].
• The proteins induced included only five proteins that have been previously associated with stress responses, consisting of endonuclease IV (Nfo), three oxyR-regulated proteins, and one heat shock protein [23].

Analytical, diagnostic and therapeutic context of oxyR

• The distribution of proteins synthesized after treatment with these agents overlapped significantly with that seen after hydrogen peroxide treatment, and it included all the proteins in the oxyR regulon [24].
• The oxyR gene from Erwinia carotovora: cloning, sequence analysis and expression in Escherichia coli [25].
• Homologs of the Escherichia coli oxyR gene were identified in several Erwinia species, using a combination of PCR and Southern hybridization analysis [25].

References