Processing of Pseudomonas exotoxin A is dispensable for cell intoxication. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Infection and Immunity Année : 2009

Processing of Pseudomonas exotoxin A is dispensable for cell intoxication.

Résumé

Exotoxin A is a major virulence factor of Pseudomonas aeruginosa. This toxin binds to a specific receptor on animal cells, allowing its endocytosis. Once in endosomes, the exotoxin can be processed by furin to generate a C-terminal toxin fragment that lacks the receptor binding domain and is retrogradely transported to the ER for retrotranslocation to the cytosol through the Sec61 channel. The toxin then blocks protein synthesis by ADP-ribosylation of elongation factor 2, thereby triggering cell death. A shorter intracellular route has also been described for this toxin. It involves direct translocation of the entire toxin from endosomes to the cytosol, and therefore does not rely on furin-mediated cleavage. To examine the implication of endosomal translocation in the intoxication process, we investigated whether this toxin required furin-mediated processing in order to kill cells. We used three different approaches. We first fused to the N-terminus of the toxin proteins with different unfolding abilities so that they would inhibit or not endosomal translocation of the chimera. We then assayed the amount of toxin fragments delivered to the cytosol during cell intoxication. Finally we used furin inhibitors and examined the fate and intracellular localization of the toxin and its receptor. The results showed that exotoxin cytotoxicity largely results from endosomal translocation of the entire toxin. We found that the C-terminal fragment was unstable within the cytosol.

Dates et versions

hal-00378977 , version 1 (27-04-2009)

Identifiants

Citer

Juliette Morlon-Guyot, Jocelyn Méré, Anne Bonhoure, Bruno Beaumelle. Processing of Pseudomonas exotoxin A is dispensable for cell intoxication.. Infection and Immunity, 2009, 77 (7), epub ahead of print. ⟨10.1128/IAI.01390-08⟩. ⟨hal-00378977⟩
87 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More