Bacterial iron detoxification at the molecular level

Bradley, Justin M.; Svistunenko, Dimitri A.; Wilson, Michael T.; Hemmings, Andrew M.; Moore, Geoffrey R.; Brun, Nick E. Le

doi:10.1074/jbc.rev120.007746

Cited by 76 publications

(74 citation statements)

References 231 publications

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“…Besides these genes, ferritin and ferric uptake regulation protein (Fur) are upregulated upon O 2 exposure in C. ljungdahlii (Whitham et al, 2015). This may indicate not only a protection mechanism focused on the control of iron availability inside the cell by Fur, repressing the genes involved in iron uptake, but also an alternative and complementary route to remove O 2 while scavenging iron via ferritin ferroxidase activity (Bradley et al, 2020), thus contributing to prevent ROS formation through Fenton chemistry. Fe-S clusters, especially of the [4Fe4S] 2+/1+ type, are highly sensitive to O 2 and/or ROS.…”

Section: Changes In Metabolism Upon O 2 Exposure In Clostridiamentioning

confidence: 99%

Responses of Clostridia to oxygen: from detoxification to adaptive strategies

Morvan

Folgosa

Kint

et al. 2021

Environmental Microbiology

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Clostridia comprise bacteria of environmental, biotechnological and medical interest and many commensals of the gut microbiota. Because of their strictly anaerobic lifestyle, oxygen is a major stress for Clostridia. However, recent data showed that these bacteria can cope with O 2 better than expected for obligate anaerobes through their ability to scavenge, detoxify and consume O 2 . Upon O 2 exposure, Clostridia redirect their central metabolism onto pathways less O 2 -sensitive and induce the expression of genes encoding enzymes involved in O 2 -reduction and in the repair of oxidized damaged molecules. While Faecalibacterium prausnitzii efficiently consumes O 2 through a specific extracellular electron shuttling system requiring riboflavin, enzymes such as rubrerythrins and flavodiiron proteins with NAD(P) H-dependent O 2 -and/or H 2 O 2 -reductase activities are usually encoded in other Clostridia. These two classes of enzymes play indeed a pivotal role in O 2 tolerance in Clostridioides difficile and Clostridium acetobutylicum. Two main signalling pathways triggering O 2 -induced responses have been described so far in Clostridia. PerR acts as a key regulator of the O 2 -and/or reactive oxygen species-defence machinery while in C. difficile, σ B , the sigma factor of the general stress response also plays a crucial role in O 2 tolerance by controlling the expression of genes involved in O 2 scavenging and repair systems.

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Section: Changes In Metabolism Upon O 2 Exposure In Clostridiamentioning

confidence: 99%

Responses of Clostridia to oxygen: from detoxification to adaptive strategies

Morvan

Folgosa

Kint

et al. 2021

Environmental Microbiology

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“…To achieve a timely response to oxidative stress, oxidative stress defense should be coordinated efficiently in which CosR, PerR, and iron play key roles. Iron is an essential micronutrient affecting bacterial growth [28], and the unavailability of iron significantly reduces the growth of C. jejuni [22,24]. Moreover, iron participates in the generation of ROS through the Fenton reaction and is also involved in the regulation of oxidative stress defense [22,24], primarily by repressing the transcription of perR in C. jejuni [11,18].…”

Section: Discussionmentioning

confidence: 99%

CosR Regulation of perR Transcription for the Control of Oxidative Stress Defense in Campylobacter jejuni

et al. 2021

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Oxidative stress resistance is an important mechanism to sustain the viability of oxygen-sensitive microaerophilic Campylobacter jejuni. In C. jejuni, gene expression associated with oxidative stress defense is modulated by PerR (peroxide response regulator) and CosR (Campylobacter oxidative stress regulator). Iron also plays an important role in the regulation of oxidative stress, as high iron concentrations reduce the transcription of perR. However, little is known about how iron affects the transcription of cosR. The level of cosR transcription was increased when the defined media MEMα (Minimum Essential Medium) was supplemented with ferrous (Fe²⁺) and ferric (Fe3⁺) iron and the Mueller–Hinton (MH) media was treated with an iron chelator, indicating that iron upregulates cosR transcription. However, other divalent cationic ions, such as Zn2+, Cu2+, Co2+, and Mn2+, did not affect cosR transcription, suggesting that cosR transcription is regulated specifically by iron. Interestingly, the level of perR transcription was increased when CosR was overexpressed. The positive regulation of perR transcription by CosR was observed both in the presence or in the absence of iron. The results of the electrophoretic mobility shift assay showed that CosR directly binds to the perR promoter. DNase I footprinting assays revealed that the CosR binding site in the perR promoter overlaps with the PerR box. In the study, we demonstrated that cosR transcription is increased in iron-rich conditions, and CosR positively regulates the transcription of PerR, another important regulator of oxidative stress defense in C. jejuni. These results provide new insight into how C. jejuni regulates oxidative stress defense by coordinating the transcription of perR and cosR in response to iron.

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“…For example, the porin-cytochrome fusion encoded by cyc2 appears nearly ubiquitous in our surveyed data; cyc2, whose phylogenetic distribution implies rampant lateral transfer among prokaryotes (McAllister et al, 2020a), may thus represent a widespread mechanism for respiratory iron oxidation. Alternatively, it is possible that Cyc2 acts as an iron detoxification mechanism (Bradley et al, 2020). In addition to porin-cytochromes, other mechanisms for iron redox were detected in diverse habitats.…”

Section: Discussionmentioning

confidence: 99%

Metagenomic Insights Into the Microbial Iron Cycle of Subseafloor Habitats

et al. 2021

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Microbial iron cycling influences the flux of major nutrients in the environment (e.g., through the adsorptive capacity of iron oxides) and includes biotically induced iron oxidation and reduction processes. The ecological extent of microbial iron cycling is not well understood, even with increased sequencing efforts, in part due to limitations in gene annotation pipelines and limitations in experimental studies linking phenotype to genotype. This is particularly true for the marine subseafloor, which remains undersampled, but represents the largest contiguous habitat on Earth. To address this limitation, we used FeGenie, a database and bioinformatics tool that identifies microbial iron cycling genes and enables the development of testable hypotheses on the biogeochemical cycling of iron. Herein, we survey the microbial iron cycle in diverse subseafloor habitats, including sediment-buried crustal aquifers, as well as surficial and deep sediments. We inferred the genetic potential for iron redox cycling in 32 of the 46 metagenomes included in our analysis, demonstrating the prevalence of these activities across underexplored subseafloor ecosystems. We show that while some processes (e.g., iron uptake and storage, siderophore transport potential, and iron gene regulation) are near-universal, others (e.g., iron reduction/oxidation, siderophore synthesis, and magnetosome formation) are dependent on local redox and nutrient status. Additionally, we detected niche-specific differences in strategies used for dissimilatory iron reduction, suggesting that geochemical constraints likely play an important role in dictating the dominant mechanisms for iron cycling. Overall, our survey advances the known distribution, magnitude, and potential ecological impact of microbe-mediated iron cycling and utilization in sub-benthic ecosystems.

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Bacterial iron detoxification at the molecular level

Cited by 76 publications

References 231 publications

Responses of Clostridia to oxygen: from detoxification to adaptive strategies

Responses of Clostridia to oxygen: from detoxification to adaptive strategies

CosR Regulation of perR Transcription for the Control of Oxidative Stress Defense in Campylobacter jejuni

Metagenomic Insights Into the Microbial Iron Cycle of Subseafloor Habitats

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