Roles of Cellular Redox Factors in Pathogen and Toxin Entry in the Endocytic Pathways

Sun, Jianjun

doi:10.5772/50087

Cited by 3 publications

(6 citation statements)

References 142 publications

(174 reference statements)

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“…Disulfide bonds are redox-controlled switches for pathogen invasion and are involved in regulating pathogen entry into the endocytic pathway of vertebrates (42) and some invertebrates (43,44). Recently, vesicle-mediated colonization of salivary glands has been suggested for CYp infection of E. variegatus (12).…”

Section: Discussionmentioning

confidence: 99%

“…Consistently, the protein disulfide-isomerase (five transcripts) and the gamma interferon-inducible lysosomal thiol genes were upregulated upon CYp infection, supporting the involvement of the endocytic pathway in phytoplasma colonization of the host, as described for Leishmania, Listeria, and Chlamydia spp. (42). Other bacterial pathogens have developed strategies to interfere with host lipidation mechanisms (45).…”

Section: Discussionmentioning

confidence: 99%

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Two Phytoplasmas Elicit Different Responses in the Insect Vector Euscelidius variegatus Kirschbaum

et al. 2018

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Phytoplasmas are plant-pathogenic bacteria transmitted by hemipteran insects. The leafhopper is a natural vector of chrysanthemum yellows phytoplasma (CYp) and a laboratory vector of flavescence dorée phytoplasma (FDp). The two phytoplasmas induce different effects on this species: CYp slightly improves whereas FDp negatively affects insect fitness. To investigate the molecular bases of these different responses, transcriptome sequencing (RNA-seq) analysis of infected with either CYp or FDp was performed. The sequencing provided the first transcriptome assembly for a phytoplasma vector and a starting point for further analyses on differentially regulated genes, mainly related to immune system and energy metabolism. Insect phenoloxidase activity, immunocompetence, and body pigmentation were measured to investigate the immune response, while respiration and movement rates were quantified to confirm the effects on energy metabolism. The activation of the insect immune response upon infection with FDp, which is not naturally transmitted by, confirmed that this bacterium is mostly perceived as a potential pathogen. Conversely, the acquisition of CYp, which is naturally transmitted by , seems to increase the insect fitness by inducing a prompt response to stress. This long-term relationship is likely to improve survival and dispersal of the infected insect, thus enhancing the opportunity of phytoplasma transmission.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Two Phytoplasmas Elicit Different Responses in the Insect Vector Euscelidius variegatus Kirschbaum

et al. 2018

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“…These toxins are also single-chain AB toxins. However, A translocates in the endoplasmic reticulum ( Figure 3 d) [ 52 ].…”

Section: Generalities About Ab Toxinsmentioning

confidence: 99%

AB Toxins as High-Affinity Ligands for Cell Targeting in Cancer Therapy

Márquez-López,

Fanarraga

2023

IJMS

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Conventional targeted therapies for the treatment of cancer have limitations, including the development of acquired resistance. However, novel alternatives have emerged in the form of targeted therapies based on AB toxins. These biotoxins are a diverse group of highly poisonous molecules that show a nanomolar affinity for their target cell receptors, making them an invaluable source of ligands for biomedical applications. Bacterial AB toxins, in particular, are modular proteins that can be genetically engineered to develop high-affinity therapeutic compounds. These toxins consist of two distinct domains: a catalytically active domain and an innocuous domain that acts as a ligand, directing the catalytic domain to the target cells. Interestingly, many tumor cells show receptors on the surface that are recognized by AB toxins, making these high-affinity proteins promising tools for developing new methods for targeting anticancer therapies. Here we describe the structure and mechanisms of action of Diphtheria (Dtx), Anthrax (Atx), Shiga (Stx), and Cholera (Ctx) toxins, and review the potential uses of AB toxins in cancer therapy. We also discuss the main advances in this field, some successful results, and, finally, the possible development of innovative and precise applications in oncology based on engineered recombinant AB toxins.

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“…A growing body of evidence suggests that cellular redox factors play essential roles in intoxication by AB toxins, by mediating the reduction of their disulphide bonds (Carle, Brink, Orth, Aktories, & Barth, 2017;Pirazzini et al, 2013;Ratts et al, 2003;Schnell et al, 2016;Sun, 2012). The maintenance of the redox potential of the cell cytosol requires a network of redox systems.…”

Section: Mbmdm Lysates Reduce Aip56 Disulphide Bond In Vitromentioning

confidence: 99%

“…Several studies established the importance of the disulphide bridge linking the A and B subunits in the toxicity of several toxins, including diphtheria toxin (DT; Falnes & Olsnes, 1995) and botulinum and tetanus neurotoxins (BoNT and TeNT;Pirazzini, Rossetto, Bolognese, Shone, & Montecucco, 2011;Schiavo, Papini, Genna, & Montecucco, 1990). Also, a growing body of evidence suggests that cellular redox factors play essential roles in intoxication by several AB toxins by mediating reduction of the interchain disulphide bridge, thereby allowing release of the A moiety at the cytosol (reviewed by Sun, 2012). Although the mechanism of disulphide reduction-dependent translocation is not fully understood and may be toxin-specific, for toxins that translocate from endosomes (such as DT, BoNT, and TeNT) what is reported is that reduction must occur at the cytosol (de Paiva et al, 1993;Falnes, Madshus, Sandvig, & Olsnes, 1992;Fischer & Montal, 2007;Madshus, Wiedlocha, & Sandvig, 1994;Schiavo et al, 1990).…”

mentioning

confidence: 99%

Role of AIP56 disulphide bond and its reduction by cytosolic redox systems for efficient intoxication

Pereira

Rodrigues

Pereira

et al. 2019

Cellular Microbiology

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Apoptosis-inducing protein of 56 kDa (AIP56) is a major virulence factor of Photobacterium damselae subsp. piscicida, a gram-negative pathogen that infects warm water fish species worldwide and causes serious economic losses in aquacultures.AIP56 is a single-chain AB toxin composed by two domains connected by an unstructured linker peptide flanked by two cysteine residues that form a disulphide bond.The A domain comprises a zinc-metalloprotease moiety that cleaves the NF-kB p65, and the B domain is involved in binding and internalisation of the toxin into susceptible cells. Previous experiments suggested that disruption of AIP56 disulphide bond partially compromised toxicity, but conclusive evidences supporting the importance of that bond in intoxication were lacking. Here, we show that although the disulphide bond of AIP56 is dispensable for receptor recognition, endocytosis, and membrane interaction, it needs to be intact for efficient translocation of the toxin into the cytosol. We also show that the host cell thioredoxin reductase-thioredoxin system is involved in AIP56 intoxication by reducing the disulphide bond of the toxin at the cytosol. The present study contributes to a better understanding of the molecular mechanisms operating during AIP56 intoxication and reveals common features shared with other AB toxins.

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Roles of Cellular Redox Factors in Pathogen and Toxin Entry in the Endocytic Pathways

Cited by 3 publications

References 142 publications

Two Phytoplasmas Elicit Different Responses in the Insect Vector Euscelidius variegatus Kirschbaum

Two Phytoplasmas Elicit Different Responses in the Insect Vector Euscelidius variegatus Kirschbaum

AB Toxins as High-Affinity Ligands for Cell Targeting in Cancer Therapy

Role of AIP56 disulphide bond and its reduction by cytosolic redox systems for efficient intoxication

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