Author, as appears in the article.: Murciano, Celia; Lee, Chung-Te; Fernandez-Bravo, Ana; Hsieh, Tsung-Han; Fouz, Belen; Hor, Lien-I; Amaro, Carmen;
Department: Ciències Mèdiques Bàsiques
URV's Author/s: Fernández Bravo, Ana
Keywords: Virulence plasmid Vibrio V. vulnificus Sepsis Rtx toxin Qpcr array Pathogen Metalloprotease Martx Infection Identification Gene expression Escherichia-coli Domain Biotype 2 Bacteria
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 MARTX(Vv) (Multifunctional-Autoprocessive-Repeats-in-Toxin; RtxA1(3)), 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 RtxA1(3) 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 rtxA1(3) deficient mutant, and a Bt1 strain (YJ016) producing RtxA1(1) (the most studied MARTX(Vv)) together with its rtxA1(1) deficient mutant, as controls. Our results showed that RtxA1(3) was essential for virulence, as R99 Delta Delta rtxA1(3) 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 RtxA1(3). 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 RtxA1(3) would act as a sepsis-inducing toxin.
Thematic Areas: Saúde coletiva Química Odontología Microbiology (medical) Microbiology Medicine (miscellaneous) Medicina veterinaria Medicina iii Medicina ii Medicina i Interdisciplinar Infectious diseases Immunology Geociências Farmacia Ensino Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências agrárias i Biotecnología Biodiversidade
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: ana.fernandez@urv.cat
Author identifier: 0000-0001-7637-5958
Record's date: 2024-09-07
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://www.frontiersin.org/articles/10.3389/fcimb.2017.00332/full
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Frontiers In Cellular And Infection Microbiology. 7
APA: Murciano, Celia; Lee, Chung-Te; Fernandez-Bravo, Ana; Hsieh, Tsung-Han; Fouz, Belen; Hor, Lien-I; Amaro, Carmen; (2017). MARTX Toxin in the Zoonotic Serovar of Vibrio vulnificus Triggers an Early Cytokine Storm in Mice. Frontiers In Cellular And Infection Microbiology, 7(), -. DOI: 10.3389/fcimb.2017.00332
Article's DOI: 10.3389/fcimb.2017.00332
Entity: Universitat Rovira i Virgili
Journal publication year: 2017
Publication Type: Journal Publications
Repositori URV