Imperial College London
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ProfessorAlainFilloux

Faculty of Natural Sciences, Department 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{Howard:2021:10.1128/mBio.00262-21,
author = {Howard, SA and Furniss, RCD and Bonini, D and Amin, H and Paracuellos, P and Zlotkin, D and R, D Costa T and Levy, A and A, I Mavridou D and Filloux, A},
doi = {10.1128/mBio.00262-21},
journal = {mBio},
pages = {1--19},
title = {The breadth and molecular basis of Hcp-driven type six secretion system (T6SS) effector delivery},
url = {http://dx.doi.org/10.1128/mBio.00262-21},
volume = {12},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The type VI secretion system (T6SS) is a bacterial nanoscale weapon that delivers toxins into prey ranging from bacteria and fungi to animal hosts. The cytosolic contractile sheath of the system wraps around stacked hexameric rings of Hcp proteins, which form an inner tube. At the tip of this tube is a puncturing device comprising a trimeric VgrG topped by a monomeric PAAR protein. The number of toxins a single system delivers per firing event remains unknown, since effectors can be loaded on diverse sites of the T6SS apparatus, notably the inner tube and the puncturing device. Each VgrG or PAAR can bind one effector, and additional effector cargoes can be carried in the Hcp ring lumen. While many VgrG- and PAAR-bound toxins have been characterized, to date, very few Hcp-bound effectors are known. Here, we used 3 known Pseudomonas aeruginosa Hcp proteins (Hcp1 to -3), each of which associates with one of the three T6SSs in this organism (H1-T6SS, H2-T6SS, and H3-T6SS), to perform in vivo pulldown assays. We confirmed the known interactions of Hcp1 with Tse1 to -4, further copurified a Hcp1-Tse4 complex, and identified potential novel Hcp1-bound effectors. Moreover, we demonstrated that Hcp2 and Hcp3 can shuttle T6SS cargoes toxic to Escherichia coli. Finally, we used a Tse1-Bla chimera to probe the loading strategy for Hcp passengers and found that while large effectors can be loaded onto Hcp, the formed complex jams the system, abrogating T6SS function.
AU  - Howard,SA
AU  - Furniss,RCD
AU  - Bonini,D
AU  - Amin,H
AU  - Paracuellos,P
AU  - Zlotkin,D
AU  - R,D Costa T
AU  - Levy,A
AU  - A,I Mavridou D
AU  - Filloux,A
DO  - 10.1128/mBio.00262-21
EP  - 19
PY  - 2021///
SN  - 2150-7511
SP  - 1
TI  - The breadth and molecular basis of Hcp-driven type six secretion system (T6SS) effector delivery
T2  - mBio
UR  - http://dx.doi.org/10.1128/mBio.00262-21
UR  - https://journals.asm.org/doi/full/10.1128/mBio.00262-21
UR  - http://hdl.handle.net/10044/1/89593
VL  - 12
ER  -
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