The Pseudomonas aeruginosa T6SS-VgrG1b spike is topped by a PAAR protein eliciting DNA damage to bacterial competitors
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
The type VI secretion system (T6SS) is a supramolecular complex involved in the delivery of potent toxins during bacterial competition. Pseudomonas aeruginosa possesses three T6SS gene clusters and several hcp and vgrG gene islands, the latter encoding the spike at the T6SS tip. The vgrG1b cluster encompasses seven genes whose organization and sequences are highly conserved in P. aeruginosa genomes, except for two genes that we called tse7 and tsi7. We show that Tse7 is a Tox-GHH2 domain nuclease which is distinct from other T6SS nucleases identified thus far. Expression of this toxin induces the SOS response, causes growth arrest and ultimately results in DNA degradation. The cytotoxic domain of Tse7 lies at its C terminus, while the N terminus is a predicted PAAR domain. We find that Tse7 sits on the tip of the VgrG1b spike and that specific residues at the PAAR–VgrG1b interface are essential for VgrG1b-dependent delivery of Tse7 into bacterial prey. We also show that the delivery of Tse7 is dependent on the H1-T6SS cluster, and injection of the nuclease into bacterial competitors is deployed for interbacterial competition. Tsi7, the cognate immunity protein, protects the producer from the deleterious effect of Tse7 through a direct protein–protein interaction so specific that toxin/immunity pairs are effective only if they originate from the same P. aeruginosa isolate. Overall, our study highlights the diversity of T6SS effectors, the exquisite fitting of toxins on the tip of the T6SS, and the specificity in Tsi7-dependent protection, suggesting a role in interstrain competition.
Date Issued
2018-12-04
Date Acceptance
2018-11-01
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2018, 115 (49), pp.12519-12524
ISSN
0027-8424
Publisher
National Academy of Sciences
Start Page
12519
End Page
12524
Journal / Book Title
Proceedings of the National Academy of Sciences of the United States of America
Volume
115
Issue
49
Copyright Statement
© 2018 Published under the PNAS license (https://www.pnas.org/page/authors/licenses.).
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000452124700057&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
MR/K001930/1
MR/M009505/1
MR/N023250/1
MR/P028225/1
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
T6SS
protein secretion
bacterial toxin
nuclease
PAAR
VI SECRETION SYSTEM
GROWTH-INHIBITION CDI
EFFECTORS
DELIVERY
TOXIN
Publication Status
Published
Date Publish Online
2018-11-19