PLoS Pathogens (Feb 2013)

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

  • 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

DOI
https://doi.org/10.1371/journal.ppat.1003128
Journal volume & issue
Vol. 9, no. 2
p. e1003128

Abstract

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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.