Abstract
Bacterial Rhs proteins containing toxic domains are often secreted by type VI secretion systems (T6SSs) through unclear mechanisms. Here, we show that the T6SS Rhs-family effector TseI of Aeromonas dhakensis is subject to self-cleavage at both the N- and the C-terminus, releasing the middle Rhs core and two VgrG-interacting domains (which we name VIRN and VIRC). VIRC is an endonuclease, and the immunity protein TsiI protects against VIRC toxicity through direct interaction. Proteolytic release of VIRC and VIRN is mediated, respectively, by an internal aspartic protease activity and by two conserved glutamic residues in the Rhs core. Mutations abolishing self-cleavage do not block secretion, but reduce TseI toxicity. Deletion of VIRN or the Rhs core abolishes secretion. TseI homologs from Pseudomonas syringae, P. aeruginosa, and Vibrio parahaemolyticus are also self-cleaved. VIRN and VIRC interact with protein VgrG1, while the Rhs core interacts with protein TecI. We propose that VIRN and the Rhs core act as T6SS intramolecular chaperones to facilitate toxin secretion and function.
Highlights
Bacterial Rhs proteins containing toxic domains are often secreted by type VI secretion systems (T6SSs) through unclear mechanisms
We previously predicted a chaperone-dependent T6SS effector TseI in Aeromonas dhakensis, a waterborne pathogen associated with skin and soft-tissue infection, gastroenteritis, and bacteremia[34,39,40]
The VIRN domain and the Rhs core are required for VIRC delivery and co-translocated by T6SS, suggesting they may function as secreted chaperones for VIRC
Summary
Bacterial Rhs proteins containing toxic domains are often secreted by type VI secretion systems (T6SSs) through unclear mechanisms. We show that the T6SS Rhs-family effector TseI of Aeromonas dhakensis is subject to self-cleavage at both the N- and the Cterminus, releasing the middle Rhs core and two VgrG-interacting domains (which we name VIRN and VIRC). We propose that VIRN and the Rhs core act as T6SS intramolecular chaperones to facilitate toxin secretion and function. Non-structural effectors can be secreted by binding to the inner Hcp tube or to the tip VgrG/PAAR proteins[10,19,33]; the latter often involves chaperone proteins that are required for stabilization and delivery of effectors[34,35,36,37,38]. The VIRN domain and the Rhs core are required for VIRC delivery and co-translocated by T6SS, suggesting they may function as secreted chaperones for VIRC. The C-terminal domain of TseI belongs to the predicted HNH Endonuclease VII toxin superfamily (pfam15657) with conserved [ED]H motif and two histidine residues (Supplementary Fig. 1)
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