The Apoptogenic Toxin AIP56 Is a Metalloprotease A-B Toxin that Cleaves NF-kappa b P65

作者：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^*

来源：PLoS Pathogens, 2013, 9(2): e1003128.

DOI：10.1371/journal.ppat.1003128

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-kappa B p65-cleaving zinc-metalloprotease whose catalytic activity is required for the apoptogenic effect. Most of the bacterial effectors known to target NF-kappa B 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-kappa B at the Cys(39)-Glu(40) peptide bond and that the C-terminal domain is involved in binding and internalization into the cytosol.

• 出版日期2013-2