Lethal oxidative damage and mutagenesis are generated by iron in delta fur mutants of Escherichia coli: protective role of superoxide dismutase

Touati, Danièle; Jacques, Mario; Tardat, Brigitte; Bouchard, Louise; Despied, S

doi:10.1128/jb.177.9.2305-2314.1995

Cited by 418 publications

(337 citation statements)

References 57 publications

(56 reference statements)

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“…Most Fur-regulated genes are derepressed in low iron concentrations and repressed when a high concentration of iron is present (Hantke, 1981;Hantke, 2002). The finding that fur mutants are sensitive to H 2 O 2 and that they suffer an increase in oxidative DNA damage leading to mutations under aerobic conditions supports the hypothesis that Fur has a role in the defense against oxidative stress (Touati et al, 1995). Furthermore, the regulators of E. coli responses to oxidative stress, OxyR and SoxRS, activate the expression of Fur and suggest that control of iron metabolism in E. coli is an integral part of the antioxidant response …”

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confidence: 52%

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Several pathways of hydrogen peroxide action that damage the E. coli genome

Asad

Almeida

et al. 2004

Genet. Mol. Biol.

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Hydrogen peroxide is an important reactive oxygen species (ROS) that arises either during the aerobic respiration process or as a by-product of water radiolysis after exposure to ionizing radiation. The reaction of hydrogen peroxide with transition metals imposes on cells an oxidative stress condition that can result in damage to cell components such as proteins, lipids and principally to DNA, leading to mutagenesis and cell death. Escherichia coli cells are able to deal with these adverse events via DNA repair mechanisms, which enable them to recover their genome integrity. These include base excision repair (BER), nucleotide excision repair (NER) and recombinational repair. Other important defense mechanisms present in Escherichia coli are OxyR and SosRS anti-oxidant inducible pathways, which are elicited by cells to avoid the introduction of oxidative lesions by hydrogen peroxide. This review summarizes the phenomena of lethal synergism between UV irradiation (254 nm) and H 2 O 2 , the cross-adaptive response between different classes of genotoxic agents and hydrogen peroxide, and the role of copper ions in the lethal response to H 2 O 2 under low-iron conditions. Key words: hydrogen peroxide, cross-adaptive response, lethal synergism, copper and iron. General AspectsThe appearance of aerobic forms of life was an important step in the evolutionary process, since oxygen consumption leads to the production of ten-fold more energy from glucose than does anaerobic metabolism (Meneghini, 1987). However, this process imposes constraints on cell viability, because of the generation of reactive oxygen species during respiration.The consecutive univalent reduction of molecular oxygen to water produces three active intermediates: superoxide anion (O 2 -• ), hydrogen peroxide (H 2 O 2 ) and hydroxyl radical (OH • ). These intermediates, collectively referred to as reactive oxygen species (ROS) are potent oxidants of lipids, proteins, and nucleic acids (Halliwell and Gutteridge, 1984;Mello-Filho and Meneghini, 1985;Meneghini, 1988). Among the oxidative DNA lesions, one of the major classes of DNA damage leads to modification in purine and pyrimidine bases, together with oligonucleotide strand breaks, DNA-protein cross-links and abasic sites. Increasing evidence suggests that the cumulative damage caused by ROS contributes to numerous degenerative diseases associated with aging, such as atherosclerosis, rheumatoid arthritis and cancer (Ames et al., 1993;Halliwell and Gutteridge, 1999).Living organisms have developed specific mechanisms to prevent the production and effects of ROS. The reduction of O 2 by cytochrome oxidase without yielding ROS, the superoxide dismutase catalysis of O 2 -• into H 2 O 2 through a dismutation reaction, the decomposition of H 2 O 2 by catalase and peroxidases, and the scavenging of ROS by some vitamins comprise part of the set of cellular antioxidant defenses (Halliwell and Gutteridge, 1999). Synthesis of the enzymes that catalyze these reactions is a part of the adaptive response tr...

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confidence: 52%

“…Pretreatment with iron chelators protects both prokaryotic and eukaryotic cells against the lethal effects of H 2 O 2 (Mello-Filho and Meneghini, 1985;Asad and Leitão, 1991). Additionally, cultures of Staphylococcus aureus are more sensitive to H 2 O 2 when iron is added to the culture media and in E. coli cultures the same is observed (Touati et al, 1995).…”

mentioning

confidence: 95%

Several pathways of hydrogen peroxide action that damage the E. coli genome

Asad

Almeida

et al. 2004

Genet. Mol. Biol.

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“…The best-characterized global regulator of iron utilization genes is Fur (for a review of Fur in Neisseria, see Rohde and Dyer [70]), and the interrelatedness of Fur regulation and oxidative stress responses have been previously described. A fur mutant of E. coli grown at increased oxygen tensions exhibited oxidative DNA damage possibly due to excess free iron generated by derepression of iron uptake genes (85). Moreover, the promoter region of fldA, the cotranscribed gene upstream of fur in E. coli, exhibits a binding site for SoxS, the positive regulator of SOD (91).…”

Section: Resultsmentioning

confidence: 99%

The OxyR Regulon in Nontypeable Haemophilus influenzae

et al. 2007

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Nontypeable Haemophilus influenzae (NTHi) is a gram-negative bacterium and a common commensal organism of the upper respiratory tract in humans. NTHi causes a number of diseases, including otitis media, sinusitis, conjunctivitis, exacerbations of chronic obstructive pulmonary disease, and bronchitis. During the course of colonization and infection, NTHi must withstand oxidative stress generated by insult due to multiple reactive oxygen species produced endogenously by other copathogens and by host cells. Using an NTHi-specific microarray containing oligonucleotides representing the 1821 open reading frames of the recently sequenced NTHi isolate 86-028NP, we have identified 40 genes in strain 86-028NP that are upregulated after induction of oxidative stress due to hydrogen peroxide. Further comparisons between the parent and an isogenic oxyR mutant identified a subset of 11 genes that were transcriptionally regulated by OxyR, a global regulator of oxidative stress. Interestingly, hydrogen peroxide induced the OxyR-independent upregulation of expression of the genes encoding components of multiple iron utilization systems. This finding suggested that careful balancing of levels of intracellular iron was important for minimizing the effects of oxidative stress during NTHi colonization and infection and that there are additional regulatory pathways involved in iron utilization.In the evolution of life, a delicate physiological balance has arisen to compensate for both an organism's need for oxygen and the attendant lethal consequences of oxygen's toxicity. For example, in the electron transport chain, electrons can be inadvertently transferred from redox-active proteins to oxygen, producing reactive oxygen species (ROS) such as superoxide and hydrogen peroxide (H 2 O 2 ). The effects of ROS on cells can then be exacerbated by the presence of free iron which, via the Fenton reaction, can react with H 2 O 2 to produce more highly reactive hydroxyl radicals (34, 40, 52). Within a host, this problem is compounded by the release of extracellular ROS by phagocytes, which again, can have deleterious effects on invading pathogens (13). Thus, bacteria have evolved an array of increasingly well-defined mechanisms to abrogate the effects of oxidative stress. Proteins involved in such processes include catalase, which decomposes H 2 O 2 , and members of both the AhpCF/TsaA family of alkylhydroperoxidases and the organic hydroperoxide resistance proteins (Ohr) that decompose organic peroxides. Also, DNA-binding ferritin-like proteins (Dps) sequester free iron and bind to DNA, thus protecting DNA from damage (27,33,45,53,59,60,67). In addition, many bacterial species possess genes encoding OxyR, a global regulator of antioxidant defenses (24, 66).Protection against oxidative stress is especially important to nontypeable Haemophilus influenzae (NTHi). NTHi is one of three bacterial commensal organisms, the others being Streptococcus pneumoniae and Moraxella catarrhalis, which can ascend a virus-compromised eustachian tube and caus...

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“…Thus, it is not surprising that perturbations of bacterial iron homeostasis often result in changes in H 2 O 2 resistance profiles. In particular, increased sensitivity to H 2 O 2 correlates with increased available cellular iron (66). The iron-activated antimicrobial streptonigrin has also been used to approximate the iron state of several bacterial species, with an increased SNG sensitivity implying an increased available cellular iron (33,43,70).…”

Section: Discussionmentioning

confidence: 99%

Antiparallel and Interlinked Control of Cellular Iron Levels by the Irr and RirA Regulators of Agrobacterium tumefaciens

Hibbing

Fuqua

2011

J Bacteriol

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The plant pathogen Agrobacterium tumefaciens encodes predicted iron-responsive regulators, Irr and RirA, that function in several other bacteria to control the response to environmental iron levels. Deletion mutations of irr and rirA, alone and in combination, were evaluated for their impact on cellular iron response. Growth was severely diminished in the ⌬irr mutant under iron-limiting conditions, but reversed to wild-type levels in an ⌬irr ⌬rirA mutant. The level of uncomplexed iron in the ⌬irr mutant was decreased, whereas the ⌬rirA mutant exhibited elevated iron levels. Sensitivity of the ⌬irr and ⌬rirA mutants to iron-activated antimicrobial compounds generally reflected their uncomplexed-iron levels. Expression of genes that encode iron uptake systems was decreased in the ⌬irr mutant, whereas that of iron utilization genes was increased. Irr function required a trihistidine repeat likely to mediate interactions with heme. Iron uptake genes were derepressed in the ⌬rirA mutant. In the ⌬irr ⌬rirA mutant, iron uptake and utilization genes were derepressed, roughly combining the phenotypes of the single mutants. Siderophore production was elevated in the rirA mutant, but most strongly regulated by an RirA-controlled sigma factor. Expression of rirA itself was regulated by Irr, RirA, and iron availability, in contrast to irr expression, which was relatively stable in the different mutants. These studies suggest that in A. tumefaciens, the Irr protein is most active under low-iron conditions, inhibiting iron utilization and activating iron acquisition, while the RirA protein is active under high-iron conditions, repressing iron uptake.

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Lethal oxidative damage and mutagenesis are generated by iron in delta fur mutants of Escherichia coli: protective role of superoxide dismutase

Cited by 418 publications

References 57 publications

Several pathways of hydrogen peroxide action that damage the E. coli genome

Several pathways of hydrogen peroxide action that damage the E. coli genome

The OxyR Regulon in Nontypeable Haemophilus influenzae

Antiparallel and Interlinked Control of Cellular Iron Levels by the Irr and RirA Regulators of Agrobacterium tumefaciens

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