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

• Published in: PLoS pathogens 2013-02, Vol.9 (2), p.e1003128-e1003128
• Main 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
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - physiology; Apoptosis Regulatory Proteins - physiology; Bacterial Toxins - metabolism; Bass; Biology; Fish Diseases - metabolism; Host-Pathogen Interactions; Leukocytes - metabolism; Leukocytes - pathology; Metalloproteases - metabolism; Photobacterium - metabolism; Recombinant Proteins; Transcription Factor RelA - metabolism; Virulence Factors - metabolism
• ISSN: 1553-7374; 1553-7366; 1553-7374
• 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-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.