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

• Type: Article in International Scientific Journal
• Date: 2013

Authors

silva, ds (Author) ICBAS; pereira, lmg (Author) Other; moreira, ar (Author) Other; ferreira-da-silva, f (Author) Other; brito, rm (Author) Other; faria, tq (Author) Other; zornetta, i (Author) Other; montecucco, c (Author) Other; oliveira, p (Author) ICBAS; azevedo, je (Author) ICBAS; pereira, pjb (Author) Other; macedo-ribeiro, s (Author) Other; do vale, a (Author) Other; dos santos, nms (Author) Other

Journal

Title: PLoS Pathogens

ISSN: 1553-7366

Publisher: Public Library of Science

Indexing

ISI Web of Knowledge - 25 Citations

Scopus - 26 Citations

Scientific classification

FOS: Natural sciences

Other information

Authenticus ID: P-006-EER

DOI: 10.1371/journal.ppat.1003128

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific