Our “Virulence Nano-Macromolecular Machinosome” (VN2M) team aims to Identify, to Understand, to Block and to Hijack bacterial nanomachines that challenge human health.

Bacterial nanomachines play a pivotal role in bacterial life processes, for the good but also for the bad. Nanoscale dynamic protein protein interaction (PPI) drives the assembly of the myriad of protein components that build these nanomachines.

Our VN2M team seeks to understand the molecular intimacy and the atomic architecture of these powerful biological nanomachines with the objective of deciphering how they work and regulate their activity.

Our knowledge is then used to develop original and “chirurgical” strategies to interfere with the assembly and functioning of the virulence nanomachines, just like a “grain of sand in the nanomachine’s gears”. Our molecules or peptides will allow to combat antibiotic-resistant bacterial infections in the future.

Ultimately, our increasing level of detail in the building of such “molecular cathedral” will feed our synthetic biology initiative to mimic and hijack such powerful engines for biotechnological applications, notably in cancer treatment.

1 – Integrative structural approach to decipher “atypical” T6SS nanomachines
2 – Molecular understanding of nanomachines crosstalk
3 – Connecting clinical to molecular microbiology: Identification nanomachines implicated in the virulence of Gram-negative bacterial pathogens
4 – Fighting multi-drug resistant bacterial pathogen by targeting a conserved virulence mechanisms: structure inspired (peptides) and high-throughput screening (molecules)
5 – Synthetic biology: artificial nanomachines for biotech/biomed applications

For more details, please visit us at VN2M Team


Inhibiting Type VI Secretion System Activity with a Biomimetic Peptide Designed To Target the Baseplate Wedge Complex

Y. Cherrak, I. Filella-Merce, V. Schmidt, D. Byrne, V. Sgoluppi, R. Chaiaheloudjou, S. Betzi, X. Morelli, M. Nilges, R. Pellarin, E. Durand

mBio 12 (2021)10.1128/mbio.01348-21

Structural basis for loading and inhibition of a bacterial T6 SS phospholipase effector by the VgrG spike

Nicolas Flaugnatti, Chiara Rapisarda, Martial Rey, Solène G Beauvois, Viet Anh Nguyen, Stéphane Canaan, Eric Durand, Julia Chamot‐rooke, E. Cascales, Rémi Fronzes, Laure Journet

EMBO Journal 39:e104129 (2020)10.15252/embj.2019104129

Structure and Activity of the Type VI Secretion System

Yassine Cherrak, Nicolas Flaugnatti, Eric Durand, Laure Journet, E. Cascales

Microbiology Spectrum 7 (2019)10.1128/microbiolspec.PSIB-0031-2019

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In situ and high-resolution Cryo-EM structure of the Type VI secretion membrane complex

Chiara Rapisarda, Yassine Cherrak, Romain Kooger, Victoria Schmidt, Riccardo Pellarin, Laureen Logger, E. Cascales, Martin Pilhofer, Eric Durand, Rémi Fronzes

EMBO Journal 38 (2019)10.15252/embj.2018100886

Biogenesis and structure of a type VI secretion baseplate

Yassine Cherrak, Chiara Rapisarda, Riccardo Pellarin, Guillaume Bouvier, Benjamin Bardiaux, Fabrice Allain, Christian Malosse, Martial Jean-Pierre Rey, Julia Chamot-Rooke, E. Cascales, Rémi Fronzes, Eric Durand

Nature Microbiology 3:1404-1416 (2018)10.1038/s41564-018-0260-1

Towards a complete structural deciphering of Type VI secretion system

van Son Nguyen, Badreddine Douzi, Eric Durand, Alain Roussel, E. Cascales, Christian Cambillau

Current Opinion in Structural Biology 49:77-84 (2018)10.1016/j.sbi.2018.01.007

Tryptophan-mediated Dimerization of the TssL Transmembrane Anchor Is Required for Type VI Secretion System Activity

Abdelrahim Zoued, Jean-Pierre Duneau, Eric Durand, Alexandre España, Laure Journet, Françoise Guerlesquin, E. Cascales

Journal of Molecular Biology 430:987-1003 (2018)10.1016/j.jmb.2018.02.008

Type VI secretion TssK baseplate protein exhibits structural similarity with phage receptor-binding proteins and evolved to bind the membrane complex

van Son Nguyen, Laureen Logger, Silvia Spinelli, Pierre Legrand, Thi Thanh Huyen Pham, Thi Trang Nhung Trinh, Yassine Cherrak, Abdelrahim Zoued, Aline Desmyter, Eric Durand, Alain Roussel, Christine Kellenberger, E. Cascales, Christian Cambillau

Nature Microbiology 2:17103 (2017)10.1038/nmicrobiol.2017.103

TssA: The cap protein of the Type VI secretion system tail

Abdelrahim Zoued, Eric Durand, Yoann G Santin, Laure Journet, Alain Roussel, Christian Cambillau, E. Cascales

BioEssays 39 (2017)10.1002/bies.201600262

Molecular Dissection of the Interface between the Type VI Secretion TssM Cytoplasmic Domain and the TssG Baseplate Component

Laureen Logger, Marie-Stéphanie Aschtgen, Marie Guérin, E. Cascales, Eric Durand

Journal of Molecular Biology 428:4424-4437 (2016)10.1016/j.jmb.2016.08.032

Salmonella Typhimurium utilizes a T6SS-mediated antibacterial weapon to establish in the host gut

Thibault G Sana, Nicolas Flaugnatti, Kyler A Lugo, Lilian H Lam, Amanda Jacobson, Virginie Baylot, Eric Durand, Laure Journet, E. Cascales, Denise M Monack

Proceedings of the National Academy of Sciences of the United States of America 113:E5044-E5051 (2016)10.1073/pnas.1608858113

Priming and polymerization of a bacterial contractile tail structure. 1" 2" 17

Abdelrahim Zoued, Eric Durand, Yannick R Brunet, Silvia Spinelli, Badreddine Douzi, Mathilde Guzzo, Nicolas Flaugnatti, Pierre Legrand, Laure Journet, Rémi Fronzes, Tam Mignot, Christian Cambillau, E. Cascales

Nature 531:59-63 (2016)10.1038/nature17182

Structure–Function Analysis of the TssL Cytoplasmic Domain Reveals a New Interaction between the Type VI Secretion Baseplate and Membrane Complexes

Abdelrahim Zoued, Chloé J Cassaro, Eric Durand, Badreddine Douzi, Alexandre España, Christian Cambillau, Laure Journet, E. Cascales

Journal of Molecular Biology 428:4413-4423 (2016)10.1016/j.jmb.2016.08.030

Biogenesis and structure of a Type VI secretion membrane core complex

Eric Durand, van Son Nguyen, Abdelrahim Zoued, Laureen Logger, Gerard Pehau-Arnaudet, Marie-Stéphanie Aschtgen, Silvia Spinelli, Aline Desmyter, Benjamin Bardiaux, Annick Dujeancourt, Alain Roussel, Christian Cambillau, E. Cascales, Rémi Fronzes

Nature 523:555-560 (2015)10.1038/nature14667

Inhibition of Type VI Secretion by an Anti-TssM Llama Nanobody

van Son Nguyen, Laureen Logger, Silvia Spinelli, Aline Desmyter, Thi Thu Hang Le, Christine Kellenberger, Badreddine Douzi, Eric Durand, Alain Roussel, E. Cascales, Christian Cambillau

PLoS ONE 10:1-14 (2015)

Crystal Structure and Self-Interaction of the Type VI Secretion Tail-Tube Protein from Enteroaggregative Escherichia coli

Badreddine Douzi, Silvia Spinelli, Stéphanie Blangy, Alain Roussel, Eric Durand, Yannick R Brunet, E. Cascales, Christian Cambillau

PLoS ONE 9:e86918 (2014)10.1371/journal.pone.0086918

VgrG, Tae, Tle, and beyond: the versatile arsenal of Type VI secretion effectors.

Eric Durand, Christian Cambillau, E. Cascales, Laure Journet

Trends Microbiol. 22:498-507 (2014)10.1016/j.tim.2014.06.004

Architecture and assembly of the Type VI secretion system.

Abdelrahim Zoued, Yannick R Brunet, Eric Durand, Marie-Stéphanie Aschtgen, Laureen Logger, Badreddine Douzi, Laure Journet, Christian Cambillau, E. Cascales

Biochim. Biophys. Acta 1843:1664-73 (2014)10.1016/j.bbamcr.2014.03.018

TssK Is a Trimeric Cytoplasmic Protein Interacting with Components of Both Phage-like and Membrane Anchoring Complexes of the Type VI Secretion System

Abdelrahim Zoued, Eric Durand, Cecilia C. Bebeacua, Yannick R Brunet, Badreddine Douzi, Christian Cambillau, E. Cascales, Laure Journet

Journal of Biological Chemistry 288:27031-27041 (2013)10.1074/jbc.M113.499772

Crystal structure of the VgrG1 actin cross-linking domain of the Vibrio cholerae type VI secretion system.

Eric Durand, Estelle Derrez, Gilles Audoly, Silvia Spinelli, Miguel Ortiz-Lombardia, Didier Raoult, E. Cascales, Christian Cambillau

Journal of Biological Chemistry 287:38190-9 (2012)10.1074/jbc.M112.390153

Structural characterization and oligomerization of the TssL protein, a component shared by bacterial type VI and type IVb secretion systems.

Eric Durand, Abdelrahim Zoued, Silvia Spinelli, Paul J H Watson, Marie-Stéphanie Aschtgen, Laure Journet, Christian Cambillau, E. Cascales

Journal of Biological Chemistry 287:14157-68 (2012)10.1074/jbc.M111.338731

The Assembly Mode of the Pseudopilus: a hallmark to distinguish a novel secretion system subtype

E. Durand, S. Alphonse, Céline Brochier-Armanet, G. Ball, Badreddine Douzi, A. Filloux, C. Bernard, R. Voulhoux

Journal of Biological Chemistry 286:24407-24416 (2011)10.1074/jbc.M111.234278

Towards a structural comprehension of bacterial type VI secretion systems: characterization of the TssJ-TssM complex of an Escherichia coli pathovar

Catarina Felisberto-Rodrigues, Eric Durand, Marie-Stéphanie Aschtgen, Stephanie Blangy, Miguel Ortiz-Lombardia, Badreddine Douzi, Christian Cambillau, E. Cascales

PLoS Pathogens 7:e1002386 (2011)10.1371/journal.ppat.1002386

Structure of the minor pseudopilin XcpW from the Pseudomonas aeruginosa type II secretion system.

Laura P Franz, Badreddine Douzi, Eric Durand, David H Dyer, Romé Voulhoux, Katrina T Forest

Acta Crystallogr. D Biol. Crystallogr. 67:124-30 (2011)10.1107/S0907444910051954

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  • National
    • Thomas Henry, CIRI Lyon
    • Xavier Morelli, CRCM Marseille
    • Fabien Garnier, CHU Limoges
    • Rodrigue Dessein, Institut Pasteur Lille
    • Marcel Hollenstein, Institut Pasteur Paris
    • Leon Espinosa, LCB Marseille
    • Christel Protière, SESSTIM Marseille
    • Riccardo Pellarin, Institut Pasteur Paris
    • Priscille Brodin, Institut Pasteur Lille
    • Pierre Berger, Institut Paoli Calmette, Marseille
    • Maxime Gualtieri, NOSOPHARM, Nîmes
    • Rémi Fronzes, IECB, Bordeaux
  • International
    • Ben D Ross, Darthmouth College, US
    • Cynthia Sears, Johns Hopkins Hospital, US
    • Mario F. Feldman, Washington Univ., US


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