Manipulating the type VI secretion system spike to shuttle passenger proteins
File(s)
Author(s)
Wettstadt, Sarah
Filloux, Alain
Type
Journal Article
Abstract
The type VI secretion system (T6SS) is a contractile injection apparatus that translocates a spike loaded with various effectors directly into eukaryotic or prokaryotic target cells. Pseudomonas aeruginosa can load either one of its three T6SSs with a variety of toxic bullets using different but specific modes. The T6SS spike, which punctures the bacterial cell envelope allowing effector transport, consists of a torch-like VgrG trimer on which sits a PAAR protein sharpening the VgrG tip. VgrG itself sits on the Hcp tube and all elements, packed into a T6SS sheath, are propelled out of the cell and into target cells. On occasion, effectors are covalent extensions of VgrG, PAAR or Hcp proteins, which are then coined “evolved” components as opposed to canonical. Here, we show how various passenger domains could be fused to the C terminus of a canonical VgrG, VgrG1a from P. aeruginosa, and be sent into the bacterial culture supernatant. There is no restriction on the passenger type, although the efficacy may vary greatly, since we used either an unrelated T6SS protein, β-lactamase, a covalent extension of an “evolved” VgrG, VgrG2b, or a Hcp-dependent T6SS toxin, Tse2. Our data further highlights an exceptional modularity/flexibility for loading the T6SS nano-weapon. Refining the parameters to optimize delivery of passenger proteins of interest would have attractive medical and industrial applications. This may for example involve engineering the T6SS as a delivery system to shuttle toxins into either bacterial pathogens or tumour cells which would be an original approach in the fight against antimicrobial resistant bacteria or cancer.
Date Issued
2020-02-26
Date Acceptance
2020-01-27
Citation
PLoS One, 2020, 15 (2), pp.1-20
ISSN
1932-6203
Publisher
Public Library of Science (PLoS)
Start Page
1
End Page
20
Journal / Book Title
PLoS One
Volume
15
Issue
2
Copyright Statement
© 2020 Wettstadt, Filloux. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URL
Sponsor
Biotechnology and Biological Sciences Research Council (BBSRC)
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:000535233700014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
BB/I019871/1
MR/K001930/1
MR/N023250/1
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
BACTERIAL TYPE VI
SUICIDE VECTOR
EFFECTOR TSE1
IDENTIFICATION
DELIVERY
COMPLEX
STRAIN
TOXIN
GENE
VGRG
Publication Status
Published
Article Number
ARTN e0228941
Date Publish Online
2020-02-26