The apoptogenic toxin AIP56 is a metalloprotease A-B toxin that cleaves NF-κb P65.

AIP56 (apoptosis-inducing protein of 56 kDa) is a major virulence factor of Photobacterium damselae piscicida (Phdp), a Gram-negative pathogen that causes septicemic infections, which are among the most threatening diseases in mariculture. The toxin triggers apoptosis of host macrophages and neutrop...

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Autores principales: Daniela S Silva, Liliana M G Pereira, Ana R Moreira, Frederico Ferreira-da-Silva, Rui M Brito, Tiago Q Faria, Irene Zornetta, Cesare Montecucco, Pedro Oliveira, Jorge E Azevedo, Pedro J B Pereira, Sandra Macedo-Ribeiro, Ana do Vale, Nuno M S dos Santos
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/1b80d696e675481aaa76b04b47e41c37
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spelling oai:doaj.org-article:1b80d696e675481aaa76b04b47e41c372021-11-18T06:06:00ZThe apoptogenic toxin AIP56 is a metalloprotease A-B toxin that cleaves NF-κb P65.1553-73661553-737410.1371/journal.ppat.1003128https://doaj.org/article/1b80d696e675481aaa76b04b47e41c372013-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23468618/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374AIP56 (apoptosis-inducing protein of 56 kDa) is a major virulence factor of Photobacterium damselae piscicida (Phdp), a Gram-negative pathogen that causes septicemic infections, which are among the most threatening diseases in mariculture. The toxin triggers apoptosis of host macrophages and neutrophils through a process that, in vivo, culminates with secondary necrosis of the apoptotic cells contributing to the necrotic lesions observed in the diseased animals. Here, we show that AIP56 is a NF-κB p65-cleaving zinc-metalloprotease whose catalytic activity is required for the apoptogenic effect. Most of the bacterial effectors known to target NF-κB are type III secreted effectors. In contrast, we demonstrate that AIP56 is an A-B toxin capable of acting at distance, without requiring contact of the bacteria with the target cell. We also show that the N-terminal domain cleaves NF-κB at the Cys(39)-Glu(40) peptide bond and that the C-terminal domain is involved in binding and internalization into the cytosol.Daniela S SilvaDaniela S SilvaLiliana M G PereiraAna R MoreiraFrederico Ferreira-da-SilvaRui M BritoTiago Q FariaIrene ZornettaCesare MontecuccoPedro OliveiraJorge E AzevedoPedro J B PereiraSandra Macedo-RibeiroAna do ValeNuno M S dos SantosPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 2, p e1003128 (2013)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
spellingShingle Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Daniela S Silva
Daniela S Silva
Liliana M G Pereira
Ana R Moreira
Frederico Ferreira-da-Silva
Rui M Brito
Tiago Q Faria
Irene Zornetta
Cesare Montecucco
Pedro Oliveira
Jorge E Azevedo
Pedro J B Pereira
Sandra Macedo-Ribeiro
Ana do Vale
Nuno M S dos Santos
The apoptogenic toxin AIP56 is a metalloprotease A-B toxin that cleaves NF-κb P65.
description AIP56 (apoptosis-inducing protein of 56 kDa) is a major virulence factor of Photobacterium damselae piscicida (Phdp), a Gram-negative pathogen that causes septicemic infections, which are among the most threatening diseases in mariculture. The toxin triggers apoptosis of host macrophages and neutrophils through a process that, in vivo, culminates with secondary necrosis of the apoptotic cells contributing to the necrotic lesions observed in the diseased animals. Here, we show that AIP56 is a NF-κB p65-cleaving zinc-metalloprotease whose catalytic activity is required for the apoptogenic effect. Most of the bacterial effectors known to target NF-κB are type III secreted effectors. In contrast, we demonstrate that AIP56 is an A-B toxin capable of acting at distance, without requiring contact of the bacteria with the target cell. We also show that the N-terminal domain cleaves NF-κB at the Cys(39)-Glu(40) peptide bond and that the C-terminal domain is involved in binding and internalization into the cytosol.
format article
author Daniela S Silva
Daniela S Silva
Liliana M G Pereira
Ana R Moreira
Frederico Ferreira-da-Silva
Rui M Brito
Tiago Q Faria
Irene Zornetta
Cesare Montecucco
Pedro Oliveira
Jorge E Azevedo
Pedro J B Pereira
Sandra Macedo-Ribeiro
Ana do Vale
Nuno M S dos Santos
author_facet Daniela S Silva
Daniela S Silva
Liliana M G Pereira
Ana R Moreira
Frederico Ferreira-da-Silva
Rui M Brito
Tiago Q Faria
Irene Zornetta
Cesare Montecucco
Pedro Oliveira
Jorge E Azevedo
Pedro J B Pereira
Sandra Macedo-Ribeiro
Ana do Vale
Nuno M S dos Santos
author_sort Daniela S Silva
title The apoptogenic toxin AIP56 is a metalloprotease A-B toxin that cleaves NF-κb P65.
title_short The apoptogenic toxin AIP56 is a metalloprotease A-B toxin that cleaves NF-κb P65.
title_full The apoptogenic toxin AIP56 is a metalloprotease A-B toxin that cleaves NF-κb P65.
title_fullStr The apoptogenic toxin AIP56 is a metalloprotease A-B toxin that cleaves NF-κb P65.
title_full_unstemmed The apoptogenic toxin AIP56 is a metalloprotease A-B toxin that cleaves NF-κb P65.
title_sort apoptogenic toxin aip56 is a metalloprotease a-b toxin that cleaves nf-κb p65.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/1b80d696e675481aaa76b04b47e41c37
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