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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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) |
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DOAJ |
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EN |
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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 |
work_keys_str_mv |
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