Survival of Escherichia coli Cells on Solid Copper Surfaces Is Increased by Glutathione

Große, Cornelia; Schleuder, Grit; Schmole, Christin; Nies, Dietrich H.

doi:10.1128/aem.02842-14

Cited by 26 publications

(38 citation statements)

References 70 publications

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“…Indeed, based on the stronger phenotype, the antiporter would be the primary means of Cu ϩ efflux from the cytoplasm, and CueA-mediated efflux would be less critical (though the cueA paralog Psest_0600 could also reduce the effects of the cueA mutation). Such a proposal is in agreement with prior suggestions both that Mrp antiporters may have other unidentified substrates (68) and also that some alkali metal ion transporters may allow some passage of Cu ϩ (62,69). The latter has been discussed in terms of entry of Cu ϩ into the cell under conditions of copper toxicity, and both proposals are without direct evidence for any specific examples.…”

Section: Resultssupporting

confidence: 74%

Novel Metal Cation Resistance Systems from Mutant Fitness Analysis of Denitrifying Pseudomonas stutzeri

Vaccaro

Lancaster

Thorgersen

et al. 2016

Appl Environ Microbiol

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Metal ion transport systems have been studied extensively, but the specificity of a given transporter is often unclear from amino acid sequence data alone. In this study, predicted Cu 2؉ IMPORTANCEIn this study, genome-wide mutant fitness data in P. stutzeri RCH2 combined with regulon predictions identify several proteins of unknown function that are involved in resisting zinc and copper toxicity. For zinc, these include a member of the UPF0016 protein family that was previously implicated in Ca 2؉ /H ؉ antiport and a human congenital glycosylation disorder, CorB and CorC, which were previously linked to Mg 2؉ transport, and Psest_3322 and Psest_0618, two proteins with no characterized homologs. Experiments using mutants lacking Psest_3226, Psest_3322, corB, corC, or czcI verified their proposed functions, which will enable future studies of these little-characterized zinc resistance determinants. Likewise, Psest_2850, annotated as an ion antiporter subunit, and the conserved hypothetical protein Psest_0584 are implicated in copper resistance. Physiological connections between previous studies and phenotypes presented here are discussed. Functional and mechanistic understanding of transport proteins improves the understanding of systems in which members of the same protein family, including those in humans, can have different functions.T he responses of microorganisms to metal toxicity have been well studied (1). In brief, metal ions can be toxic by binding to essential proteins or other molecules, causing them to become nonfunctional or function incorrectly. This occurs, for example, where the toxic metal ion binds to a binding site that requires a different metal ion to function. Toxic metal ions can also catalyze reactions that are detrimental to the cell, such as hydroxyl radical generation catalyzed by free iron (Fe 3ϩ/2ϩ ) (2) or iron-sulfur cluster degradation by copper (3).Understanding modes of toxicity and metal resistance systems is important, as the information gained from bacteria can be applied to human physiology and medicine. For example, Wilson's disease and Menkes disease are two human diseases caused by mutations in copper transporters (4). Likewise, acrodermatitis enteropathica, while less well-studied at a mechanistic level, is caused by a mutation of the SLC39A4 zinc transporter gene (5). Wilson's disease results in copper accumulation, which is known to cause tissue damage due to the generation of reactive oxygen species (4). Similarly, copper and zinc are known to be involved in neurodegenerative diseases, such as Alzheimer's and Parkinson's, again with a connection to oxidative stress, although their precise roles are still unclear (6). In addition, copper has long been used as

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Section: Resultssupporting

confidence: 74%

Novel Metal Cation Resistance Systems from Mutant Fitness Analysis of Denitrifying Pseudomonas stutzeri

Vaccaro

Lancaster

Thorgersen

et al. 2016

Appl Environ Microbiol

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“…Gram-negative organisms (18,19). However, under the anaerobic conditions employed here, GSH renders L. lactis more sensitive to copper, particularly during the first phase of exponential growth.…”

Section: Discussionmentioning

confidence: 94%

“…It is found in a limited number of bacteria (13), in which it can be either synthesized or taken up from the medium. GSH has been shown to exert a major protective effect toward oxidative stress and acid stress, as well as the toxicity of arsenite, copper, and other heavy metal ions (14)(15)(16)(17)(18). When Streptococcus pneumoniae was allowed to take up GSH from the environment, it became more resistant to copper but also to the non-redox-active heavy metals cadmium and zinc (19).…”

mentioning

confidence: 99%

Mechanism of Attenuation of Uranyl Toxicity by Glutathione in Lactococcus lactis

Obeid

Oertel

Solioz

et al. 2016

Appl Environ Microbiol

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b ABSTRACTBoth prokaryotic and eukaryotic organisms possess mechanisms for the detoxification of heavy metals, and these mechanisms are found among distantly related species. We investigated the role of intracellular glutathione (GSH), which, in a large number of taxa, plays a role in protection against the toxicity of common heavy metals. Anaerobically grown Lactococcus lactis containing an inducible GSH synthesis pathway was used as a model organism. Its physiological condition allowed study of putative GSH-dependent uranyl detoxification mechanisms without interference from additional reactive oxygen species. By microcalorimetric measurements of metabolic heat during cultivation, it was shown that intracellular GSH attenuates the toxicity of uranium at a concentration in the range of 10 to 150 M. In this concentration range, no effect was observed with copper, which was used as a reference for redox metal toxicity. At higher copper concentrations, GSH aggravated metal toxicity. Isothermal titration calorimetry revealed the endothermic binding of U(VI) to the carboxyl group(s) of GSH rather than to the reducing thiol group involved in copper interactions. The data indicate that the primary detoxifying mechanism is the intracellular sequestration of carboxyl-coordinated U(VI) into an insoluble complex with GSH. The opposite effects on uranyl and on copper toxicity can be related to the difference in coordination chemistry of the respective metal-GSH complexes, which cause distinct growth phase-specific effects on enzyme-metal interactions. IMPORTANCEUnderstanding microbial metal resistance is of particular importance for bioremediation, where microorganisms are employed for the removal of heavy metals from the environment. This strategy is increasingly being considered for uranium. However, little is known about the molecular mechanisms of uranyl detoxification. Existing studies of different taxa show little systematics but hint at a role of glutathione (GSH). Previous work could not unequivocally demonstrate a GSH function in decreasing the presumed uranyl-induced oxidative stress, nor could a redox-independent detoxifying action of GSH be identified. Combining metabolic calorimetry with cell number-based assays and genetics analysis enables a novel and general approach to quantify toxicity and relate it to molecular mechanisms. The results show that GSH-expressing microorganisms appear advantageous for uranyl bioremediation.T he natural abundance of uranium and the increasing health risks that originate from its anthropogenic release to the environment have generated a high demand for understanding the molecular mechanisms of uranium toxicity. Its radiotoxicity is of minor ecological relevance compared to its toxicity due to chemical interference with metabolism (1, 2). The latter is caused mostly by the displacement of Ca 2ϩ and Mg 2ϩ from functionally important binding sites in enzymes (3). The water-soluble uranyl cation UO 2 2ϩ is the most commonly found contaminant, which contains uranium in its highest ...

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“…This contrasts sharply with the transcriptional regulator HrtR, the haem-regulated transporter regulator, which binds haem and induces DNA dissociation and transcriptional derepression of a haem-efflux system in L. lactis [173,174]. Finally a putative Cu-responsive TetR has been identified as ComR in E. coli [175,176]. Although it is clear that ComR is involved in the Cu stress response in some way, direct Cu binding by ComR has not yet been reported.…”

Section: Other Metalloregulatory Protein Familiesmentioning

confidence: 99%

Metallochaperones and metalloregulation in bacteria

Capdevila

Edmonds

Giedroc

2017

Essays in Biochemistry

105

117

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Bacterial transition metal homoeostasis or simply ‘metallostasis’ describes the process by which cells control the intracellular availability of functionally required metal cofactors, from manganese (Mn) to zinc (Zn), avoiding bothmetal deprivation and toxicity. Metallostasis is an emerging aspect of the vertebrate host–pathogen interface that is defined by a ‘tug-of-war’ for biologically essential metals and provides the motivation for much recent work in this area. The host employs a number of strategies to starve the microbial pathogen of essential metals, while for others attempts to limit bacterial infections by leveraging highly competitive metals. Bacteria must be capable of adapting to these efforts to remodel the transition metal landscape and employ highly specialized metal sensing transcriptional regulators, termed metalloregulatory proteins, and metallochaperones, that allocate metals to specific destinations, to mediate this adaptive response. In this essay, we discuss recent progress in our understanding of the structural mechanisms and metal specificity of this adaptive response, focusing on energy-requiring metallochaperones that play roles in the metallocofactor active site assembly in metalloenzymes and metallosensors, which govern the systems-level response to metal limitation and intoxication.

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Survival of Escherichia coli Cells on Solid Copper Surfaces Is Increased by Glutathione

Cited by 26 publications

References 70 publications

Novel Metal Cation Resistance Systems from Mutant Fitness Analysis of Denitrifying Pseudomonas stutzeri

Novel Metal Cation Resistance Systems from Mutant Fitness Analysis of Denitrifying Pseudomonas stutzeri

Mechanism of Attenuation of Uranyl Toxicity by Glutathione in Lactococcus lactis

Metallochaperones and metalloregulation in bacteria

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