James Imlay

..Their failure to divest themselves of enzymes that can be directly damaged by molecular oxygen suggests that evolution has not yet provided economical options to them...

..Thus, the history of Fe-S clusters is an unusual one that has profoundly shaped contemporary microbial ecology...

..Current research seeks to identify these, and bacteria comprise an exceptionally accessible experimental system that has provided many of the answers. This manuscript reviews recent developments and identifies remaining puzzles...

..The vulnerability of cells to oxidation lies at the root of obligate anaerobiosis, spontaneous mutagenesis, and the use of oxidative stress as a biological weapon...

..Some potential benefits of superoxide reduction have been proposed; these and several others are considered here...

..Evidently, oxidative defences in anaerobes can be robust. In all likelihood, they are critical for the movement of bacteria through aerobic environments to new anaerobic habitats...

..The rate constant of the Fenton reaction measured at physiological pH was much higher than under the acidic conditions that were used to determine the commonly cited value...

..Accordingly, during H2O2 stress, mutants that cannot import manganese and/or are unable to sequester iron suffer high rates of protein oxidation...

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..The induction of Fur synthesis by the OxyR response comprises one evolutionary solution to that problem...

..coli synthesizes a transport system. Thus, AcnB may be retained as the primary aconitase because the lability of its exposed cluster allows E. coli to sense and respond to iron depletion...

..More generally, this study provides a new example of a situation in which the vulnerability of cells to oxidative DNA damage is strongly affected by their physiological state...

..The extreme vulnerability of these enzymes may explain why many organisms, including mammals, deploy H2O2 to suppress microbial growth...

..Our results indicate that wattle condensed tannins are toxic to E. coli in aerobic medium primarily because they generate H(2)O(2). The oxidative stress response helps E. coli strains to overcome their inhibitory effect...

..That source has not yet been identified. In respiring cells the rate of H2O2 production was approximately 0.5% the rate of total oxygen consumption, with only modest changes when cells used different carbon sources...

..Further, mutants that lack flavin reductase were resistant to NO/H2O2, and overproducing strains were hypersensitive. We discuss the possibility that H2O2 and NO synergize when macrophages attack captive bacteria...

..These observations do not explain how copper suppresses iron-mediated damage. However, it is clear that copper does not catalyze significant oxidative DNA damage in vivo; therefore, copper toxicity must occur by a different mechanism...

..Copper efflux by dedicated export systems, chelation by glutathione, and cluster repair by assembly systems all enhance the resistance of cells to this metal...

..In contrast, succinate dehydrogenase, with high potential clusters, generates O2*- exclusively. The identities of enzyme autoxidation products are significant because O2*- and H2O2 damage cells in different ways...

..It is hoped that the resolution of these issues will lead to an understanding of stress resistance that is more accurate and perceptive...

..These two examples reveal biochemical and physiological arrangements through which evolution has minimized the rate of intracellular oxidant formation...

..coli when respiration is blocked. It remains unclear whether flavins or other reductants drive Fenton chemistry in respiring cells...

..One role of periplasmic SOD may be to avert this damage. In contrast, periplasmic SOD was ineffective at lowering the extracellular super-oxide concentration and, therefore, may have little impact upon HOONO formation...

..We propose that this novel property of SodCI is crucial to its ability to contribute to virulence in serovar Typhimurium...

..coli. This endogenous superoxide may create oxidative stress in that compartment and be a primary substrate of CuZnSOD...

..We propose a model to account for the various properties of SodCI and how they contribute to bacterial survival in the phagosome...

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..This proposal represents an abrupt departure from conventional models, and it will attract further experimental tests...

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..pneumoniae has a novel mechanism to avoid the toxic effects of the Fenton reaction...

..Our results suggest the possibility that the beneficial effects of some of the so-called "SOD mimic drugs" may be due to some property other than in vivo superoxide dismutase activity...

..coli will provide a blueprint for efforts to solve key issues in oxidative stress: obligate anaerobiosis, the killing mechanism of) hagocytes, and endogenous oxidative stress in higher organisms. ..

..Further, by understanding how metabolic perturbations affect DNA oxidation, we may be able to anticipate the affects of drug therapies upon mutagenesis and cell death. ..

..Other, such as glucose-6-phosphate dehydrogenases, may be understandable only if some of the toxicity of these drugs arises from NADPH depletion rather than from reactive oxygen species. ..