Relevance of peroxiredoxins in pathogenic microorganisms

Oliveira, Marcos Antônio de; Tairum, Carlos A.; Netto, Luís Eduardo Soares; Oliveira, Ana; Aleixo-Silva, Rogerio Luis; Cabrera, Vitoria Isabela Montanhero; Breyer, Carlos Alexandre; Santos, M. C. dos

doi:10.1007/s00253-021-11360-5

Cited by 14 publications

(14 citation statements)

References 155 publications

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“…Prxs specifically decompose several kinds of hydroperoxides, including H 2 O 2 , by providing reducing equivalents. In return, thioredoxin serves as an electron donor for Prxs [ 1 , 8 , 35 ]. In Acanthamoeba , four Prxs were identified in the genome [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…In Candida glabrata and S. cerevisiae , one Prx was described as the main Prx against ROS, while another was proposed to be a backup [ 16 , 31 ]. Alternatively, Prx-2 and Prx-3 might fulfil other functions, since Prxs were also reported to contribute to genome stability or function as chaperones reviewed by de Oliveira et al [ 8 ]. A more detailed evaluation also on the protein level will be needed to gain greater insights into the metabolism of Prxs in Acanthamoeba spp.…”

Section: Discussionmentioning

confidence: 99%

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Transcriptional changes of proteins of the thioredoxin and glutathione systems in Acanthamoeba spp. under oxidative stress – an RNA approach

et al. 2022

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The thioredoxin (Trx) and the glutathione (GSH) systems represent important antioxidant systems in cells and in particular thioredoxin reductase (TrxR) has been shown to constitute a promising drug target in parasites. For the facultative protozoal pathogen Acanthamoeba, it was demonstrated that a bacterial TrxR as well as a TrxR, characteristic of higher eukaryotes, mammals and humans is expressed on the protein level. However, only bacterial TrxR is strongly induced by oxidative stress in Acanthamoeba castellanii. In this study, the impact of oxidative stress on key enzymes involved in the thioredoxin and the glutathione system of A. castellanii under different culture conditions and of clinical Acanthamoeba isolates was evaluated on the RNA level employing RT-qPCR. Additionally, the effect of auranofin, a thioredoxin reductase inhibitor, already established as a potential drug in other parasites, on target enzymes in A. castellanii was investigated. Oxidative stress induced by hydrogen peroxide led to significant stimulation of bacterial TrxR and thioredoxin, while diamide had a strong impact on all investigated enzymes. Different strains displayed distinct transcriptional responses, rather correlating to sensitivity against the respective stressor than to respective pathogenic potential. Culture conditions appear to have a major effect on transcriptional changes in A. castellanii. Treatment with auranofin led to transcriptional activation of the GSH system, indicating its role as a potential backup for the Trx system. Altogether, our data provide more profound insights into the complex redox system of Acanthamoeba, preparing the ground for further investigations on this topic.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Transcriptional changes of proteins of the thioredoxin and glutathione systems in Acanthamoeba spp. under oxidative stress – an RNA approach

et al. 2022

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“…We note that PRX classification based on active site profiles has been adopted in recent literature, such as 46 and 47 , although there still are exceptions, such as 48,49,50,51 . Continuing challenges are the incorrect, vague or ambiguous annotations in online gene databases, in addition to annotations based on older nomenclature thus does not easily correspond with current literature 41,45 .…”

Section: Peroxiredoxins (Prx)mentioning

confidence: 99%

Antioxidant enzymes that target hydrogen peroxide are conserved across the animal kingdom, from sponges to mammals

Hewitt

Degnan

2023

Sci Rep

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Oxygen is the sustenance of aerobic life and yet is highly toxic. In early life, antioxidants functioned solely to defend against toxic effects of reactive oxygen species (ROS). Later, as aerobic metabolisms evolved, ROS became essential for signalling. Thus, antioxidants are multifunctional and must detoxify, but also permit ROS signalling for vital cellular processes. Here we conduct metazoan-wide genomic assessments of three enzymatic antioxidant families that target the predominant ROS signaller, hydrogen peroxide: namely, monofunctional catalases (CAT), peroxiredoxins (PRX), and glutathione peroxidases (GPX). We reveal that the two most evolutionary ancient families, CAT and PRX, exhibit metazoan-wide conservation. In the basal animal lineage, sponges (phylum Porifera), we find all three antioxidant families, but with GPX least abundant. Poriferan CATs are distinct from bilaterian CATs, but the evolutionary divergence is small. Amongst PRXs, subfamily PRX6 is the most conserved, whilst subfamily AhpC-PRX1 is the largest; PRX4 is the only core member conserved from sponges to mammals and may represent the ancestral animal AhpC-PRX1. Conversely, for GPX, the most recent family to arise, only the cysteine-dependent subfamily GPX7 is conserved across metazoans, and common across Porifera. Our analyses illustrate that the fundamental functions of antioxidants have resulted in gene conservation throughout the animal kingdom.

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“…Some of these redox relays have implications in mitigating oxidative stress and/or transducing redox signals, whereas others aid in the correct formation of structural disulfides within proteins. Oxidative stress and alterations in oxidative protein folding are thought to contribute to bacterial virulence, inflammation, age-related pathologies (including cancer and neurodegenerative diseases), and the aging process, itself, all of which establish the significance of understanding the role these disulfide exchange pathways play in both homeostasis and disease. − As a result, many of the disulfide redox relays described below represent potential targets for treating microbial infections, cancers, and degenerative diseases associated with aberrant protein folding and protein secretion. ,− …”

Section: Prominent Disulfide Redox Relays In Cellsmentioning

confidence: 99%

Experimental Approaches for Investigating Disulfide-Based Redox Relays in Cells

West

2022

Chem. Res. Toxicol.

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Reversible oxidation of cysteine residues within proteins occurs naturally during normal cellular homeostasis and can increase during oxidative stress. Cysteine oxidation often leads to the formation of disulfide bonds, which can impact protein folding, stability, and function. Work in both prokaryotic and eukaryotic models over the past five decades has revealed several multiprotein systems that use thiol-dependent oxidoreductases to mediate disulfide bond reduction, formation, and/or rearrangement. Here, I provide an overview of how these systems operate to carry out disulfide exchange reactions in different cellular compartments, with a focus on their roles in maintaining redox homeostasis, transducing redox signals, and facilitating protein folding. Additionally, I review thiol-independent and thiol-dependent approaches for interrogating what proteins partner together in such disulfide-based redox relays. While the thiol-independent approaches rely either on predictive measures or standard procedures for monitoring protein−protein interactions, the thiol-dependent approaches include direct disulfide trapping methods as well as thiol-dependent chemical cross-linking. These strategies may prove useful in the systematic characterization of known and newly discovered disulfide relay mechanisms and redox switches involved in oxidant defense, protein folding, and cell signaling.

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Relevance of peroxiredoxins in pathogenic microorganisms

Cited by 14 publications

References 155 publications

Transcriptional changes of proteins of the thioredoxin and glutathione systems in Acanthamoeba spp. under oxidative stress – an RNA approach

Transcriptional changes of proteins of the thioredoxin and glutathione systems in Acanthamoeba spp. under oxidative stress – an RNA approach

Antioxidant enzymes that target hydrogen peroxide are conserved across the animal kingdom, from sponges to mammals

Experimental Approaches for Investigating Disulfide-Based Redox Relays in Cells

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