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 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 cys39-glu40 peptide bond and that the c-terminal domain is involved in binding and internalization into the cytosol. © 2013 silva et al.