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MARTX Toxin in the Zoonotic Serovar of Vibrio vulnificus Triggers an Early Cytokine Storm in Mice

Overview of attention for article published in Frontiers in Cellular and Infection Microbiology, July 2017
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Title
MARTX Toxin in the Zoonotic Serovar of Vibrio vulnificus Triggers an Early Cytokine Storm in Mice
Published in
Frontiers in Cellular and Infection Microbiology, July 2017
DOI 10.3389/fcimb.2017.00332
Pubmed ID
Authors

Murciano, Celia, Lee, Chung-Te, Fernández-Bravo, Ana, Hsieh, Tsung-Han, Fouz, Belén, Hor, Lien-I, Amaro, Carmen

Abstract

Vibrio vulnificus biotype 2-serovar E is a zoonotic clonal complex that can cause death by sepsis in humans and fish. Unlike other biotypes, Bt2 produces a unique type of MARTXVv (Multifunctional-Autoprocessive-Repeats-in-Toxin; RtxA13), which is encoded by a gene duplicated in the pVvBt2 plasmid and chromosome II. In this work, we analyzed the activity of this toxin and its role in human sepsis by performing in vitro, ex vivo, and in vivo assays. First, we demonstrated that the ACD domain, present exclusively in this toxin variant, effectively has an actin-cross-linking activity. Second, we determined that the whole toxin caused death of human endotheliocytes and monocytes by lysis and apoptosis, respectively. Finally, we tested the hypothesis that RtxA13 contributes to human death caused by this zoonotic serovar by triggering an early cytokine storm in blood. To this end, we used a Bt2-SerE strain (R99) together with its rtxA13 deficient mutant, and a Bt1 strain (YJ016) producing RtxA11 (the most studied MARTXVv) together with its rtxA11 deficient mutant, as controls. Our results showed that RtxA13 was essential for virulence, as R99ΔΔrtxA13 was completely avirulent in our murine model of infection, and that R99, but not strain YJ016, induced an early, strong and dysregulated immune response involving the up-regulation of a high number of genes. This dysregulated immune response was directly linked to RtxA13. Based on these results and those obtained ex vivo (human blood), we propose a model of infection for the zoonotic serovar of V. vulnificus, in which RtxA13 would act as a sepsis-inducing toxin.

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Mendeley readers

The data shown below were compiled from readership statistics for 5 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 5 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 3 60%
Student > Master 1 20%
Student > Bachelor 1 20%
Readers by discipline Count As %
Immunology and Microbiology 2 40%
Agricultural and Biological Sciences 1 20%
Biochemistry, Genetics and Molecular Biology 1 20%
Medicine and Dentistry 1 20%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 July 2017.
All research outputs
#10,199,462
of 11,495,107 outputs
Outputs from Frontiers in Cellular and Infection Microbiology
#1,138
of 1,421 outputs
Outputs of similar age
#220,469
of 261,660 outputs
Outputs of similar age from Frontiers in Cellular and Infection Microbiology
#119
of 143 outputs
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So far Altmetric has tracked 1,421 research outputs from this source. They receive a mean Attention Score of 3.7. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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