The apoptogenic toxin AIP56 is a metalloprotease A-B toxin that cleaves NF-κb P65.
2013
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
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.
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