Inhibition of Cholera Toxin and Other AB Toxins by Polyphenolic Compounds

Cherubin, Patrick; Garcia, Maria Camila; Curtis, D. R.; Britt, Christopher B. T.; Craft, John W.; Burress, Helen; Berndt, C. C.; Reddy, Srikar; Guyette, Jessica; Zheng, Tianyu; Huo, Qun; Quiñones, Beatriz; Briggs, James M.; Teter, Ken

doi:10.1371/journal.pone.0166477

Cited by 32 publications

(34 citation statements)

References 45 publications

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“…We have previously reported a direct, proportional link between the specific loss of d2EGFP fluorescence and the overall loss of protein synthesis in a population of toxin-treated cells 20 . Subsequent studies further documented the usefulness of the Vero-d2EGFP cells for measuring the activity of AB toxins 17 , 21 – 24 . Other investigators have used similar cell-based toxicity assays with destabilized reporters 25 – 27 and have documented a direct correlation between the toxin-induced inhibition of total protein synthesis and the toxin-induced loss of reporter signal 28 .…”

Section: Resultsmentioning

confidence: 96%

Cellular recovery from exposure to sub-optimal concentrations of AB toxins that inhibit protein synthesis

Cherubin

Quiñones

Teter

2018

Sci Rep

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Ricin, Shiga toxin, exotoxin A, and diphtheria toxin are AB-type protein toxins that act within the host cytosol and kill the host cell through pathways involving the inhibition of protein synthesis. It is thought that a single molecule of cytosolic toxin is sufficient to kill the host cell. Intoxication is therefore viewed as an irreversible process. Using flow cytometry and a fluorescent reporter system to monitor protein synthesis, we show a single molecule of cytosolic toxin is not sufficient for complete inhibition of protein synthesis or cell death. Furthermore, cells can recover from intoxication: cells with a partial loss of protein synthesis will, upon removal of the toxin, increase the level of protein production and survive the toxin challenge. Thus, in contrast to the prevailing model, ongoing toxin delivery to the cytosol appears to be required for the death of cells exposed to sub-optimal toxin concentrations.

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Section: Resultsmentioning

confidence: 96%

Cellular recovery from exposure to sub-optimal concentrations of AB toxins that inhibit protein synthesis

Cherubin

Quiñones

Teter

2018

Sci Rep

Self Cite

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“…Grape extracts inhibited the cholera intoxication in cultured cells and intestinal loops through various actions, including the elimination of the pre-bound toxin from the cell surfaces, and disruption of the unfolding, transport and catalytic activities of the dissociated A subunit [152]. In a later study, the function of 20 individual phenolic constituents of grape extracts in cholera toxin inhibition was assessed [153]. Among others, inhibitory functions affecting the toxin binding and the enzyme activity have been associated with the mode of action of individual phenolic compounds.…”

Section: Anti-enterotoxin Effect Of Plant Phenolicsmentioning

confidence: 99%

Plant Phenolics and Phenolic-Enriched Extracts as Antimicrobial Agents against Food-Contaminating Microorganisms

et al. 2020

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Phenolic compounds and extracts with bioactive properties can be obtained from many kinds of plant materials. These natural substances have gained attention in the food research as possible growth inhibitors of foodborne pathogenic and spoilage bacteria. Many phenolic-enriched plant extracts and individual phenolics have promising anti-quorum sensing potential as well and can suppress the biofilm formation and toxin production of food-related pathogens. Various studies have shown that plant phenolics can substitute or support the activity of synthetic food preservatives and disinfectants, which, by the way, can provoke serious concerns in consumers. In this review, we will provide a brief insight into the bioactive properties, i.e., the antimicrobial, anti-quorum sensing, anti-biofilm and anti-enterotoxin activities, of plant phenolic extracts and compounds, with special attention to pathogen microorganisms that have food relation. Carbohydrase aided applications to improve the antimicrobial properties of phenolic extracts are also discussed.

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“…Such approach led to the identification of a set of lead compounds capable of inhibiting ChT and ExoA, and CTX exotoxin ART activity both in vitro and in cell-based assays [294]. Further, additional strategies have instead exploited the antimicrobial protection provided by polyphenolic compounds from grape extract [295]; the screening of individual compounds has led to identify twelve molecules active against CTX, where four out of twelve acting through inhibition of ART activity. Similarly, molecules inhibiting ExoS ART activity with an IC 50 of 1.3 µM have been proposed as starting point for a precise targeting of virulence factors [296].…”

Section: Conclusion: Targeting Toxin Adp-ribosyl Transferase Activitymentioning

confidence: 99%

Targeting ADP-ribosylation as an antimicrobial strategy

Catara

Corteggio

Valente

et al. 2019

Biochemical Pharmacology

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A B S T R A C T ADP-ribosylation (ADPr) is an ancient reversible modification of cellular macromolecules controlling major biological processes as diverse as DNA damage repair, transcriptional regulation, intracellular transport, immune and stress responses, cell survival and proliferation. Furthermore, enzymatic reactions of ADPr are central in the pathogenesis of many human diseases, including infectious conditions. By providing a review of ADPr signalling in bacterial systems, we highlight the relevance of this chemical modification in the pathogenesis of human diseases depending on host-pathogen interactions. The post-antibiotic era has raised the need to find alternative approaches to antibiotic administration, as major pathogens becoming resistant to antibiotics. An in-depth understanding of ADPr reactions provides the rationale for designing novel antimicrobial strategies for treatment of infectious diseases. In addition, the understanding of mechanisms of ADPr by bacterial virulence factors offers important hints to improve our knowledge on cellular processes regulated by eukaryotic homologous enzymes, which are often involved in the pathogenesis of human diseases.T large number of worldwide spread diseases, affecting humans, insects and plants [31,[56][57][58], with a great impact on human health. In addition, infectious diseases strongly affect the world economy in terms of costs for the human health as well as food and agricultural economic losses [59]. The use of antibiotics to counteract the pathogen infections has represented the therapeutic strategy of choice in the last century, however the emergence of antibiotic resistance strains represents the major challenge of the 21st century [60][61][62]. Targeting bacterial pathogenic mechanisms by disarming pathogens of virulence factors, for instance by inhibiting the enzymatic activity of bART, represents a valid alternative intervention strategy to overcome antibiotic resistance [63][64][65][66]. In addition, because of the conservation of ADPr systems throughout the evolution, the understanding of bacterial pathogenic mechanisms may contribute to unveil novel and conserved cellular processes regulated by ADPr in high organisms [34,45,67,68]. The dysregulation of such processes can be either cause of human diseases or be target of therapeutic intervention [39,[69][70][71].Herein, we will provide a summary of bacterial ADPr systems describing their pathogenic mechanisms and highlighting the similarities with ADPr systems in mammals as well. Further, we discuss the potential of targeting ADPr for therapeutic strategies of infection diseases. ADP-ribosylation in pathophysiologyADPr was originally described in the 60s; two independent studies reported the identification of a new polymer, poly(ADP-ribose) (PAR) synthesised from NAD + in vertebrate cells [72] and, simultaneously, the finding that bacterial DTX activity from C. diphteriae is dependent on NAD + content [73]. In the following decades, research in the field has expanded the involvement of ADPr ...

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Inhibition of Cholera Toxin and Other AB Toxins by Polyphenolic Compounds

Cited by 32 publications

References 45 publications

Cellular recovery from exposure to sub-optimal concentrations of AB toxins that inhibit protein synthesis

Cellular recovery from exposure to sub-optimal concentrations of AB toxins that inhibit protein synthesis

Plant Phenolics and Phenolic-Enriched Extracts as Antimicrobial Agents against Food-Contaminating Microorganisms

Targeting ADP-ribosylation as an antimicrobial strategy

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