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.
CITATION STYLE
Silva, D. S., Pereira, L. M. G., Moreira, A. R., Ferreira-da-Silva, F., Brito, R. M., Faria, T. Q., … dos Santos, N. M. S. (2013). The Apoptogenic Toxin AIP56 Is a Metalloprotease A-B Toxin that Cleaves NF-κb P65. PLoS Pathogens, 9(2). https://doi.org/10.1371/journal.ppat.1003128
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