Myeloperoxidase-mediated damage to the succinate oxidase system of Escherichia coli. Evidence for selective inactivation of the dehydrogenase component.
Myeloperoxidase, a granule-associated enzyme of neutrophils and monocytes, combines with H2O2 and chloride to form a potent microbicidal system that contributes to phagocyte antimicrobial activity. The nature of the lesion or lesions induced by the myeloperoxidase system which are responsible for the loss of microbial replicative activity (viability) remains unknown. Using Escherichia coli grown to late log or stationary phase under conditions of low aeration with succinate as the sole carbon source, we found that myeloperoxidase-induced loss of microbial viability could be correlated with a decrease in succinate-dependent respiration (succinate oxidase activity). Succinate dehydrogenase activity fell rapidly to undetectable levels during incubation with the myeloperoxidase system, suggesting that damage to the dehydrogenase was a major factor in the loss of oxidase activity. Other components of the succinate oxidase system were resistant to the actions of myeloperoxidase. The ubiquinone-8 and cytochrome components of the respiratory chain remained nearly constant in amount despite reduction of respiration to undetectable levels. However, as expected from the loss of succinate dehydrogenase activity, succinate-ubiquinone reductase and succinate-cytochrome reductase activities were markedly impaired. We propose that the loss of E. coli viability induced by the myeloperoxidase-H2O2-chloride system is due in part to the loss of electron transport function consequent to the oxidation of critical catalytic centers in susceptible dehydrogenases.
Rosen
H
H
Department of Medicine, University of Washington School of Medicine, Seattle.
Rakita
R M
RM
Waltersdorph
A M
AM
Klebanoff
S J
SJ
D004579:Electron Transport; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D007700:Kinetics; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D009195:Peroxidase / Q000494:pharmacology*; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors*; D014451:Ubiquinone / Q000378:metabolism
D014451:Ubiquinone; D010088:Oxidoreductases; C022691:succinate oxidase; D009195:Peroxidase; D013385:Succinate Dehydrogenase