Synergistic lethal effect between hydrogen peroxide and neocuproine (2,9-dimethyl 1,10-phenanthroline) in Escherichia coli

Almeida, Carlos Eduardo Bonacossa de; Felício, D.L.; Galhardo, Rodrigo S.; Cabral‐Neto, Januário B.; Leitão, Álvaro C.

doi:10.1016/s0921-8777(98)00064-0

Cited by 13 publications

(8 citation statements)

References 34 publications

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“…However, the addition of extracellular or cell-penetrating iron and copper chelators (dipyridyl, desferal, neocuproine and ferrozine) had no positive effect on viability of the Δ cymR mutant after an H 2 O 2 challenge (data not shown). This suggests more complex mechanisms of altered stress response in addition to the Fenton reaction-mediated process, as recently proposed for other microorganisms [48], [49]. High cysteine levels are correlated with the production of H 2 S by cysteine desulfhydrases (MccB, MetC, and CysM) (Fig.…”

Section: Discussionsupporting

confidence: 68%

The Pleiotropic CymR Regulator of Staphylococcus aureus Plays an Important Role in Virulence and Stress Response

et al. 2010

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We have characterized a novel pleiotropic role for CymR, the master regulator of cysteine metabolism. We show here that CymR plays an important role both in stress response and virulence of Staphylococcus aureus. Genes involved in detoxification processes, including oxidative stress response and metal ion homeostasis, were differentially expressed in a ΔcymR mutant. Deletion of cymR resulted in increased sensitivity to hydrogen peroxide-, disulfide-, tellurite- and copper-induced stresses. Estimation of metabolite pools suggests that this heightened sensitivity could be the result of profound metabolic changes in the ΔcymR mutant, with an increase in the intracellular cysteine pool and hydrogen sulfide formation. Since resistance to oxidative stress within the host organism is important for pathogen survival, we investigated the role of CymR during the infectious process. Our results indicate that the deletion of cymR promotes survival of S. aureus inside macrophages, whereas virulence of the ΔcymR mutant is highly impaired in mice. These data indicate that CymR plays a major role in virulence and adaptation of S. aureus for survival within the host.

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Section: Discussionsupporting

confidence: 68%

The Pleiotropic CymR Regulator of Staphylococcus aureus Plays an Important Role in Virulence and Stress Response

et al. 2010

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“…However, the addition of an iron chelator (dipyridyl) had no positive effect on the viability of the DcymR mutant after a paraquat or an H 2 O 2 challenge (data not shown). This suggests more complex mechanisms of stress in addition to the Fenton reaction-mediated process, as proposed recently for other microorganisms (Almeida et al, 1999;Macomber et al, 2007). H 2 S also increases the formation of H 2 O 2 and other ROS (Lloyd, 2006).…”

Section: Discussionsupporting

confidence: 68%

Complex phenotypes of a mutant inactivated for CymR, the global regulator of cysteine metabolism in Bacillus subtilis

Hullo

Martin‐Verstraete

Soutourina

2010

FEMS Microbiology Letters

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We characterized various phenotypes of a mutant inactivated for CymR, the master regulator of cysteine metabolism in Bacillus subtilis. The deletion of cymR resulted in impaired growth in the presence of cystine and increased sensitivity to hydrogen peroxide-, disulfide-, paraquat- and tellurite-induced stresses. Estimation of metabolite pools suggested that these phenotypes could be the result of profound metabolic changes in the DeltacymR mutant including an increase of the intracellular cysteine pool and hydrogen sulfide formation, as well as a depletion of branched-chain amino acids.

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“…As mentioned above, Almeida et al (1999) showed that prior incubation of fpg, uvrA and lexA mutant strains with neocuproine led to an increased sensitivity to H 2 O 2 . The chemistry of this synergistic lethal interaction was suggested to occur via the iron-mediated Fenton reaction, which would be responsible for displacement of copper ions from the complex Neo 2 Cu + , as Florence et al, (1985) have reported to occur in vitro.…”

Section: Lethal Synergism Between Phenanthrolines and H 2 Omentioning

confidence: 62%

“…However, detected a strong lethal interaction when xthA mutant cells were treated simultaneously with H 2 O 2 and o-phenanthroline. In the same way Almeida et al (1999) have also detected a lethal synergistic interaction between neocuproine (2,9-dimethyl 1,10-phenanthroline) and H 2 O 2 . In both cases the phenomenon of synergism was accompanied by an increase in the number of DNA strand breaks.…”

Section: Lethal Synergism Between Phenanthrolines and H 2 Omentioning

confidence: 73%

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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Synergistic lethal effect between hydrogen peroxide and neocuproine (2,9-dimethyl 1,10-phenanthroline) in Escherichia coli

Cited by 13 publications

References 34 publications

The Pleiotropic CymR Regulator of Staphylococcus aureus Plays an Important Role in Virulence and Stress Response

The Pleiotropic CymR Regulator of Staphylococcus aureus Plays an Important Role in Virulence and Stress Response

Complex phenotypes of a mutant inactivated for CymR, the global regulator of cysteine metabolism in Bacillus subtilis

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

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