Imperial College London

ProfessorAlainFilloux

Faculty of Natural SciencesDepartment of Life Sciences

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 9651a.filloux Website CV

 
 
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Location

 

1.47Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wettstadt:2020:10.1371/journal.pone.0228941,
author = {Wettstadt, S and Filloux, A},
doi = {10.1371/journal.pone.0228941},
journal = {PLoS One},
pages = {1--20},
title = {Manipulating the type VI secretion system spike to shuttle passenger proteins},
url = {http://dx.doi.org/10.1371/journal.pone.0228941},
volume = {15},
year = {2020}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - 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.
AU - Wettstadt,S
AU - Filloux,A
DO - 10.1371/journal.pone.0228941
EP - 20
PY - 2020///
SN - 1932-6203
SP - 1
TI - Manipulating the type VI secretion system spike to shuttle passenger proteins
T2 - PLoS One
UR - http://dx.doi.org/10.1371/journal.pone.0228941
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000535233700014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228941
UR - http://hdl.handle.net/10044/1/88359
VL - 15
ER -