Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/109792
Title: The apoptogenic toxin AIP56 is a metalloprotease A-B toxin that cleaves NF-κb P65
Authors: Silva, Daniela S.
Pereira, Liliana M. G.
Moreira, Ana R.
Ferreira-da-Silva, Frederico
Brito, Rui M. 
Faria, Tiago Q. 
Zornetta, Irene
Montecucco, Cesare
Oliveira, Pedro
Azevedo, Jorge E.
Pereira, Pedro J. B.
Macedo-Ribeiro, Sandra 
do Vale, Ana
dos Santos, Nuno M. S.
Issue Date: Feb-2013
Publisher: Public Library of Science
Project: Daniela S. Silva and Liliana M. G. Pereira were funded by FCT fellowships SFRH/BD/35865/2007 and SFRH/BD/43501/2008, respectively. Ana do Vale was supported by Programa Cieˆncia – funded by POPH - QREN - Tipologia 4.2 - Promoc¸a˜o do Emprego Cientı´fico, co-funded by Fundo Social Europeu and National funding from MCTES. This work was supported by FCT projects PTDC/BIA-PRO/101111/2008, PTDC/CVT/099544/2008 PTDC/MAR/101143/2008 and PEst-C/SAU/ LA0002/2011 (EU-FEDER funding through COMPETE). 
Serial title, monograph or event: PLoS Pathogens
Volume: 9
Issue: 2
Abstract: 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.
URI: https://hdl.handle.net/10316/109792
ISSN: 1553-7374
DOI: 10.1371/journal.ppat.1003128
Rights: openAccess
Appears in Collections:FCTUC Química - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

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