A family of diverse Kunitz inhibitors from Echinococcus granulosus potentially involved in host-parasite cross-talk. - RIIP - Réseau International des Instituts Pasteur Accéder directement au contenu
Article Dans Une Revue PLoS ONE Année : 2009

A family of diverse Kunitz inhibitors from Echinococcus granulosus potentially involved in host-parasite cross-talk.

Résumé

The cestode Echinococcus granulosus, the agent of hydatidosis/echinococcosis, is remarkably well adapted to its definitive host. However, the molecular mechanisms underlying the successful establishment of larval worms (protoscoleces) in the dog duodenum are unknown. With the aim of identifying molecules participating in the E. granulosus-dog cross-talk, we surveyed the transcriptomes of protoscoleces and protoscoleces treated with pepsin at pH 2. This analysis identified a multigene family of secreted monodomain Kunitz proteins associated mostly with pepsin/H(+)-treated worms, suggesting that they play a role at the onset of infection. We present the relevant molecular features of eight members of the E. granulosus Kunitz family (EgKU-1 - EgKU-8). Although diverse, the family includes three pairs of close paralogs (EgKU-1/EgKU-4; EgKU-3/EgKU-8; EgKU-6/EgKU-7), which would be the products of recent gene duplications. In addition, we describe the purification of EgKU-1 and EgKU-8 from larval worms, and provide data indicating that some members of the family (notably, EgKU-3 and EgKU-8) are secreted by protoscoleces. Detailed kinetic studies with native EgKU-1 and EgKU-8 highlighted their functional diversity. Like most monodomain Kunitz proteins, EgKU-8 behaved as a slow, tight-binding inhibitor of serine proteases, with global inhibition constants (K(I) (*)) versus trypsins in the picomolar range. In sharp contrast, EgKU-1 did not inhibit any of the assayed peptidases. Interestingly, molecular modeling revealed structural elements associated with activity in Kunitz cation-channel blockers. We propose that this family of inhibitors has the potential to act at the E. granulosus-dog interface and interfere with host physiological processes at the initial stages of infection.
Fichier principal
Vignette du fichier
gonzalez_journal.pone.0007009.pdf (1.32 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

pasteur-00508939 , version 1 (04-11-2010)

Identifiants

Citer

Silvia González, Martín Fló, Mariana Margenat, Rosario Durán, Gualberto González-Sapienza, et al.. A family of diverse Kunitz inhibitors from Echinococcus granulosus potentially involved in host-parasite cross-talk.. PLoS ONE, 2009, 4 (9), pp.e7009. ⟨10.1371/journal.pone.0007009⟩. ⟨pasteur-00508939⟩
114 Consultations
212 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More