Our research team focuses towards understanding the molecular basis of virulence mechanisms of the model organism, Pseudomonas aeruginosa.
P. aeruginosa is an opportunistic Gram-negative pathogen and is responsible for a wide variety of human diseases ranging from acute infections in hospital, to chronic colonization of the respiratory tract of cystic fibrosis patients. The main difficulties in treatment of patients infected with P. aeruginosa are a multi-resistance to antibiotics and a great adaptation capacity of the pathogen, which lead to the synthesis of many toxic products promoting host invasion and colonization and spread throughout the body.
Antivirulence strategies that can be developed from the characterization of virulence determinants are thus key to fight against P. aeruginosa. Its virulence is multi-factorial and we particularly focus on exported or secreted products, also called effectors, which contribute greatly to P. aeruginosa virulence by facilitating colonization and survival in the eukaryotic host or competition with other bacteria. Several effectors using the Tat export pathway or the H2-T6 secretion system are under study in the lab.
We investigate their characterization by multidisciplinary approaches of molecular microbiology, genetics, biochemistry and cell biology and through collaborations for microscopy and structural biology. We would like to address the mechanism of action of these effectors, their partners in the bacteria and their targets in the host.
Members
Researchers
- Dr G. Michel (1992 – 2010) CR1 CNRS
- Pr A. Lazdunski (1985 – 2008) Professeur – Univ. Aix-Marseille II –
Post doctoral researchers
- Dr B. Ize (2008 – 2010) – FRM Post-doc
- Title of the project : Role of the Tat system in P. aeruginosa virulence
- Now CNRS Researcher in S. Bleves’s lab (LISM-Marseille)
- Dr E. Durand (2008 – 2010) – ANR post doc- 3D Pilus
- Title of the project : Structure-function study of the Xcp pseudopilins in P. aeruginosa
- Now INSERM Researcher at the LISM-Marseille
- Dr A. Hachani (2005 – 2007) – Post-doc on a contract from the Ministry of Research to welcome researchers from abroad
Technical staff
- A. Courbois (2020-2021) – AMIDEX funded – Aix-Marseille University –
PhD students
- B. Berni (2015-2019) – MRT funded – Aix-Marseille University –
- Title of the PhD : Caractérisation et mécanisme de sécrétion d’un nouvel effecteur d’une machinerie de sécrétion de type VI- chez P. aeruginosa – Viva September 2019.
- M. Gimenez (2014-2018) – MRT funded – Aix-Marseille University –
- Title of the PhD : Role of the P. aeruginosa Tat system: identification of substrates and role in twitching motility – Viva the 17th of December 2018.
- A. Laubier (2011 – 2014) – VLM funded – Aix-Marseille University –
- Title of the PhD : The Patatin-like proteins, novel lipolytic toxins of Pseudomonas aeruginosa : potential targets against infection ? – Viva on the 3rd of october 2014.
- T. Sana (2009-2013) – MRT funded – Aix-Marseille University –
- Title of the PhD : Caracterisation of two type VI secretion systems in Pseudomonas aeruginosa: Cross-regulation and role in the microtubules-dependant invasion of non-phagocytic cells – Viva the 20th of June 2013.
- R . Salacha (2006 – 2010) – MRT funded – University of Aix-Marseille II –
- Title of the PhD : Patatins of P. aeruginosa: secreted or not secreted ? That is the question ? – Viva on the 11th of June 2010.
- P. Nogueira-Orlandi (2001 – 2004) – CNPq funded, Brazil. Viva in January 2004
Master 2 students
- S. Djermoun (2018) – Aix-Marseille University – MBVB Master 2 student – Now PhD student in Christian Lesterlin’s lab (Lyon)
- O. Chabiron (2017) – Aix-Marseille University – MBVB Master 2 student
- R. Bouharaoua (2016) – Aix-Marseille University – MBVB Master 2 student
- B. Berni (2015) – Aix-Marseille University – MBVB Master 2 student
- V. Tutagata (2014) – Aix-Marseille University – MBVB Master 2 student
- M. Gimenez (2013) – Aix-Marseille University – MBVB Master 2 student
- E. Boulant (2012) – Aix-Marseille University – MBVB Master 2 student
- P. Imbert (2011) – University of Aix-Marseille II – MBVB Master 2 student – Now Post doc in Pr. S. Grinstein’s lab (Toronto – Canada)
- T. Sana (2010) – University of Aix-Marseille II – MBVB Master 2 student
- A. Aguzzi (2008) – University of Aix-Marseille II – MBVB Master 2 student
- V. Viarre (2006) – University of Aix-Marseille II – MBVB Master 2 student
- R. Salacha (2006) – University of Aix-Marseille II – MBVB Master 2 student
- S. Reig (2003) – University of Aix-Marseille II – DEA student
Undergraduates
- D. Moulin (2022) – Aix-Marseille University – M1 student
- F. Debard (2022) – 4ème année de pharmacie faculté de Lyon
- D. Planez (2022) – Aix-Marseille University – L2 student
- E. Esnault (2021) – Polytech student (Marseille)
- C. Cibien (2021) – Aix-Marseille University – MBVB Master 1 student
- M. Schiano (2019) – High school student 2nd Lycée Sainte Trinité (Marseille)
- B. Cardoso (2019) – Aix-Marseille University – L2 student
- M. Cortiggiani (2019) – Aix-Marseille University – L3 student
- M. Hachemane (2019) – Aix-Marseille University – MBVB Master 1 student
- A. Nabonnand (2018) – Aix-Marseille University – L3 student
- C. Aubéry (2018) – High school student 3ème Collège du Thors (Vaucluse)
- R. Lacombe (2018) – High school student 3ème Collège de Pernes les fontaines (Vaucluse)
- M. Ghazaryan (2018) – High school student 3ème Collège de Provence (Marseille)
- G. Lextrait (2018) – Aix-Marseille University – L3 student
- M. Sarrazin (2018) – Aix-Marseille University – MBVB Master 1 student – Now M2 student in S. Canaan’s team (LISM- Marseille)
- D. Popoff (2017) – Aix-Marseille University – L3 student
- Y. Thibaudeau (2017) – Aix-Marseille University – L3 student
- A. Litnari (2016) – Aix-Marseille University – Sécurité sanitaire des aliments Master 1 student
- Y. Hassoun (2016) – Aix-Marseille University – MBVB Master 1 student
- C. Raynaud (2016) – Aix-Marseille University – MBVB Master 1 student
- S. Jaussaud (2016) – Aix-Marseille University – L3 student
- I. Rajaobelina (2016) – Aix-Marseille University – L3 student BHB
- S. Poquet (2015) – Aix-Marseille University – MBVB Master 1 student
- E. Voilin (2015) – Polytech student
- S. Chautard (2015) – Polytech student
- N. Tchilian (2015) – University of Aix-Marseille II – L1 student
- A. Gaubert (2014) – Aix-Marseille University – MBVB Master 1 student
- S. Chautard (2014) – Polytech student
- L. Pariente (2014) – High school student 2nd Lycée Sainte Trinité (Marseille)
- P. Kara (2014) – High school student 2nd Lycée Sainte Trinité (Marseille)
- M. Gimenez (2013) – Aix-Marseille University – MBVB Master 1 student
- G. Urbain (2013) – Aix-Marseille University – MBVB Master 1 student
- C. Chauvet (2013) – Polytech student
- L. Villiers (2013) – Polytech student
- J. Darmon (2013) – High school student 3ème collège Sylvain Menu (Marseille)
- B. Péan (2012) – High school student 3ème collège G. Brassens (Montpellier)
- S. Wild-Chopinet (2011) – High school student Stagiaire de 3ème collège Chevreuil (Marseille)
- D. Ranada (2011) – University of Aix-Marseille II – MBVB Master 1 student – Now Post doc in R. Ieva’ lab (CBI-Toulouse)
- C. Tonglet (2010-2011) – University of Aix-Marseille II – L2/L3 student
- A. Gagnaire (2010) – University of Aix-Marseille II – L2 student
- P. Van Overvelt (2010) – University of Aix-Marseille II – MBVB Master 1 student
- R. Zoued (2010) – University of Aix-Marseille II – MBVB Master 1 student – Now Post doc in M. Waldor’s lab (BWH-Boston)
- C. Champion (2009) – University of Aix-Marseille II – MBVB Master 1 student
- E. Carpentier (2008) – University of Aix-Marseille II – ESIL student
- T. Herpin (2008) – University of Aix-Marseille II – L3 student
- F. Kovacic (2008) – Antibiotarget network PhD student
Pseudomonas team 2009-2016
- Dr R. Voulhoux (2004-) – DR2 CNRS –
- G. Ball (1986-) – IE CNRS –
- Pr Kathrina Forest (2015) visiting researcher with IMERA
- Dr B. Douzi (2015-2017) – Post doc – ANR funded
- N. Gomez (2016-) – PhD student VLM funded – Aix-Marseille University
- C. Raynaud (2017) – MBVB Master 2 student – Aix-Marseille University
- S. Lhospice (2015-2016) IE – ANR funded
- S. Michel (2012-2016) – PhD MRT funded – Aix-Marseille University – (2016-2017) – ATER – Aix-Marseille University –
- Title of the PhD : P……. Viva on the 18th of December 2017
- F. Cadoret (2010 – 2013) – PhD MRT funded – Aix-Marseille University (2013-2014) – ATER – Aix-Marseille University –
- Title of the PhD : PA7, an atypical strain of Pseudomonas aeruginosa: Transcriptomic study and caracterisation of a third functional T2SS, Txc. Viva on the 7th of july 2014.
- B. Douzi (2008 – 2011) – Fellowship from Tunisia (BDI) – University of Aix-Marseille II –
- Title of the PhD : Type II secretion system of P. aeruginosa : interactome and structure function relationship – Viva the 28th of Octobre 2011.
- V. Viarre (2006 – 2010) – MRT funded – University of Aix-Marseille II –
- Title of the PhD : The Hxc type II secretion system of Pseudomonas aeruginosa, caracterisation and functional study of the liposecretine HxcQ. Viva the 25th of June 2010.
Publications
2022
What Is New in the Anti–Pseudomonas aeruginosa Clinical Development Pipeline Since the 2017 WHO Alert?
Sébastien Reig, Audrey Le Gouellec, Sophie Bleves
Frontiers in Cellular and Infection Microbiology 12 (2022)10.3389/fcimb.2022.909731
2021
Disruption of the Pseudomonas aeruginosa Tat system perturbs PQS-dependent quorum sensing and biofilm maturation through lack of the Rieske cytochrome bc1 sub-unit
Eliza Ye-Chen Soh, Frances Smith, Maxime Rémi Gimenez, Liang Yang, Rebecca Munk Vejborg, Matthew Fletcher, Nigel Halliday, Sophie Bleves, Stephan Heeb, Miguel Cámara, Michael Givskov, Kim Hardie, Tim Tolker-Nielsen, Bérengère Ize, Paul Williams
PLoS Pathogens 17:e1009425 (2021)10.1371/journal.ppat.1009425
2020
Bacterial injection machines: Evolutionary diverse but functionally convergent
Sophie Bleves, Jorge E Galán, Matxalen Llosa
Cellular Microbiology e13157 (2020)10.1111/cmi.13157
2020
Editorial: Protein Export and Secretion Among Bacterial Pathogens
Thibault G Sana, Romé Voulhoux, Denise M Monack, Bérengère Ize, Sophie Bleves
Frontiers in Cellular and Infection Microbiology 9 (2020)10.3389/fcimb.2019.00473
2019
A Type VI Secretion System trans- kingdom effector is required for the delivery of a novel antibacterial toxin in Pseudomonas aeruginosa
Benjamin Berni, Chantal Soscia, Sarah Djermoun, Bérengère Ize, Sophie Bleves
Frontiers in Microbiology (2019)10.3389/fmicb.2019.01218
2019
Killing from the inside: Intracellular role of T3SS in the fate of Pseudomonas aeruginosa within macrophages revealed by mgtC and oprF mutants
Preeti Garai, Laurence Berry, Malika Moussouni, Sophie Bleves, Anne-Béatrice Blanc-Potard
PLoS Pathogens 15:e1007812 (2019)10.1371/journal.ppat.1007812
2019
Activity of a Synthetic Peptide Targeting MgtC on Pseudomonas aeruginosa Intramacrophage Survival and Biofilm Formation
Malika Moussouni, Pauline Nogaret, Preeti Garai, Bérengère Ize, Eric Vivès, Anne-Béatrice Blanc-Potard
Frontiers in Cellular and Infection Microbiology 9:84 (2019)10.3389/fcimb.2019.00084
2019
Differential modulation of Quorum-Sensing signaling through QslA in Pseudomonas
Thibault Gery Sana, Rodrigo Lomas, Maxime Rémi Gimenez, Aurélie Laubier, Chantal Soscia, Claire Chauvet, Ana Conesa, Romé Voulhoux, Bérengère Ize, Sophie Bleves
Journal of Bacteriology (2019)
2018
United we stand, divided we fall
Sophie Bleves, Benjamin Berni
Nature Microbiology (2018)10.1038/s41564-018-0130-x
2018
Genome wide identification and experimental validation of Pseudomonas aeruginosa Tat substrates
Maxime Rémi Gimenez, Govind Chandra, Perrine van Overvelt, Romé Voulhoux, Sophie Bleves, Bérengère Ize
Scientific Reports 8:11950 (2018)10.1038/s41598-018-30393-x
2017
Don't judge a book by its cover: The Hcps are not only structural components of the T6SS machinery
Sophie Bleves
Virulence 8:1053-1054 (2017)10.1080/21505594.2017.1295908
2017
Pseudomonas aeruginosa zinc uptake in chelating environment is primarily mediated by the metallophore pseudopaline
Sebastien Lhospice, Nicolas Oswaldo Gomez, Laurent Ouerdane, Catherine Brutesco, Ghassan Ghssein, Christine Hajjar, Ahmed Liratni, Shuanglong Wang, Pierre Richaud, Sophie Bleves, Geneviève Ball, Elise Borezée-Durant, Ryszard Lobinski, David Pignol, Pascal Arnoux, Romé Voulhoux
Scientific Reports 7:1-10 (2017)10.1038/s41598-017-16765-9
2017
Characterization of the Porphyromonas gingivalis Type IX Secretion Trans-envelope PorKLMNP Core Complex
Maxence S Vincent, Mickaël J Canestrari, Philippe Leone, Julien Stathopulos, Bérengère Ize, Abdelrahim Zoued, Christian Cambillau, Christine Kellenberger, Alain Roussel, E. Cascales
Journal of Biological Chemistry 292:3252-3261 (2017)10.1074/jbc.M116.765081
2016
Contribution of the Twin Arginine Translocation system to the exoproteome of Pseudomonas aeruginosa.
Geneviève Ball, Haike Antelmann, Paul Roger Claude Imbert, Maxime Rémi Gimenez, Romé Voulhoux, Bérengère Ize
Scientific Reports 6:27675 (2016)10.1038/srep27675
2016
Game of Trans-Kingdom Effectors
Sophie Bleves
Trends in Microbiology 24:773-774 (2016)10.1016/j.tim.2016.08.002
2016
Structural Basis of Lipid Targeting and Destruction by the Type V Secretion System of Pseudomonas aeruginosa.
Paulo Vinicius da Mata Madeira, Samira Zouhir, Pauline Basso, David Neves, Aurélie Laubier, Richard Salacha, Sophie Bleves, Eric Faudry, Carlos Contreras-Martel, Andréa Dessen
Journal of Molecular Biology 428:1790-803 (2016)10.1016/j.jmb.2016.03.012
2016
Correction: Functional Characterization of Pseudomonas Contact Dependent Growth Inhibition (CDI) Systems.
Chryslène Mercy, Bérengère Ize, Suzana P Salcedo, Sophie De Bentzmann, Sarah Bigot
PLoS ONE 11:e0150538 (2016)10.1371/journal.pone.0150538
2016
Functional Characterization of Pseudomonas Contact Dependent Growth Inhibition (CDI) Systems
Chryslène Mercy, Bérengère Ize, Suzana Pinto Salcedo, Sophie de Bentzmann, Sarah Bigot
PLoS ONE 11:e0147435 (2016)10.1371/journal.pone.0147435
2016
The T6SSs of Pseudomonas aeruginosa Strain PAO1 and Their Effectors: Beyond Bacterial-Cell Targeting.
Thibault G Sana, Benjamin Berni, Sophie Bleves
Frontiers in Cellular and Infection Microbiology 6:61 (2016)10.3389/fcimb.2016.00061
2015
A Macrophage Subversion Factor Is Shared by Intracellular and Extracellular Pathogens
Claudine Belon, Chantal Soscia, Audrey Bernut, Aurélie Laubier, Sophie Bleves, Anne-Béatrice Blanc-Potard
PLoS Pathogens 11:e1004969 (2015)10.1371/journal.ppat.1004969
2015
Intracellular phase for an extracellular bacterial pathogen: MgtC shows the way
Audrey Bernut, Claudine Belon, Chantal Soscia, Sophie Bleves, Anne-Béatrice Blanc-Potard
Microbial Cell 2:353-355 (2015)10.15698/mic2015.09.227
2015
Internalization of Pseudomonas aeruginosa Strain PAO1 into Epithelial Cells Is Promoted by Interaction of a T6SS Effector with the Microtubule Network
Thibault G. Sana, Christoph Baumann, Andreas Merdes, Chantal Soscia, Thomas Rattei, Abderrahman Hachani, Cerith Jones, Keiryn L. Bennett, Alain Filloux, Giulio Superti-Furga, Romé Voulhoux, Sophie Bleves
mBio 6 (2015)
2015
Genome-wide Screen of Pseudomonas aeruginosa in Saccharomyces cerevisiae Identifies New Virulence Factors.
Rafat Zrieq, Thibault G Sana, Sandra Vergin, Steve Garvis, Irina Volfson, Sophie Bleves, Romé Voulhoux, Johannes H Hegemann
Frontiers in Cellular and Infection Microbiology 5:81 (2015)10.3389/fcimb.2015.00081
2014
HoPaCI-DB: host-Pseudomonas and Coxiella interaction database.
Sophie Bleves, Irmtraud Dunger, Mathias C Walter, Dimitrios Frangoulidis, Gabi Kastenmüller, Romé Voulhoux, Andreas Ruepp
Nucleic Acids Research 42:D671-6 (2014)10.1093/nar/gkt925
2014
The target cell genus does not matter.
Sophie Bleves, Thibault G Sana, Romé Voulhoux
Trends Microbiol. 22:304-6 (2014)10.1016/j.tim.2014.04.011
2014
Cell fractionation.
Bérengère Ize, Véronique Viarre, Romé Voulhoux
Methods in Molecular Biology 1149:185-91 (2014)10.1007/978-1-4939-0473-0_15
2014
Gene transfer: conjugation.
Thibault G Sana, Aurélie Laubier, Sophie Bleves
Methods in Molecular Biology 1149:17-22 (2014)10.1007/978-1-4939-0473-0_3
2013
Dissecting the machinery that introduces disulfide bonds in Pseudomonas aeruginosa.
Isabelle S Arts, Geneviève Ball, Pauline Leverrier, Steven Garvis, Valérie Nicolaes, Didier Vertommen, Bérengère Ize, Veronica Tamu Dufe, Joris Messens, Romé Voulhoux, Jean-Francois Collet
mBio 4:e00912-13 (2013)10.1128/mBio.00912-13
2013
Divergent control of two type VI secretion systems by RpoN in Pseudomonas aeruginosa
Thibault G Sana, Chantal Soscia, Céline M Tonglet, Steve Garvis, Sophie Bleves
PLoS ONE 8:e76030 (2013)10.1371/journal.pone.0076030
2012
The second type VI secretion system of Pseudomonas aeruginosa strain PAO1 is regulated by quorum sensing and Fur and modulates internalization in epithelial cells.
Thibault G Sana, Abderrahman Hachani, Iwona Bucior, Chantal Soscia, Steve Garvis, Elise Termine, Joanne Engel, Alain Filloux, Sophie Bleves
Journal of Biological Chemistry 287:27095-105 (2012)10.1074/jbc.M112.376368
2011
Type VI secretion system in Pseudomonas aeruginosa: secretion and multimerization of VgrG proteins.
Abderrahman Hachani, Nadine S Lossi, Alexander Hamilton, Cerith Jones, Sophie Bleves, David Albesa-Jové, Alain Filloux
Journal of Biological Chemistry 286:12317-27 (2011)10.1074/jbc.M110.193045
2011
Role of fimV in type II secretion system-dependent protein secretion of Pseudomonas aeruginosa on solid medium.
Gérard P F Michel, Anthony Aguzzi, Geneviève Ball, Chantal Soscia, Sophie Bleves, Romé Voulhoux
Microbiology (Reading, Engl.) 157:1945-54 (2011)10.1099/mic.0.045849-0
2006
Multiple sensors control reciprocal expression of Pseudomonas aeruginosa ezgulatory RNA and virulence genes.
Isabelle Ventre, Al Goodman, Isabelle Vallet-Gely, Perrine Vasseur, Chantal Soscia, Sören Molin, Sophie Bleves, Andrée Lazdunski, Steve Lory, Alain Filloux
Proceedings of the National Academy of Sciences of the United States of America 103:171-176 (2006)
2001
Translocation of Jellyfish Green Fluorescent Protein via the Tat System of Escherichia coli and Change of Its Periplasmic Localization in Response to Osmotic Up-shock
Claire-Lise Santini, Alain Bernadac, Bérengère Ize, Carlos Blanco, Long-Fei Wu
Journal of Biological Chemistry 276:8159-8164 (2001)10.1074/jbc.C000833200
2001
Involvement of the twin-arginine translocation system in protein secretion via the type II pathway
Romé Voulhoux, Genevieve Ball, Bérengère Ize, Michael L Vasil, Andrée Lazdunski, Long-Fei Wu, Alain Filloux
EMBO Journal 20:6735-6741 (2001)10.1093/emboj/20.23.6735
1999
Assembly of XcpR in the Cytoplasmic Membrane Is Required for Extracellular Protein Secretion in Pseudomonas aeruginosa
Genevieve Ball, Virginie Chapon, Sophie Bleves, Gérard Michel, Marc Bally
Journal of Bacteriology 181:382-388 (1999)
Collaborations
- National
- Dr Anne Blanc-Pottard, CNRS, Montpellier
- Dr Stéphane Canaan, LISM, Marseille
- Dr Olivier Genest, BIP, Marseille
- Dr Marianne Ilbert, BIP, Marseille
- Dr Andreas Merdes, CNRS & Université Paul Sabatier, Toulouse
- Dr David O’Callaghan, Nîmes
- Dr Guy Schoehn, IBS, Grenoble
- Dr Mustapha Si-Tahar, INSERM U1100 Tours
- International
- Pr Paul Williams, Centre for Biomolecular Sciences, Nottingham, UK
- Dr Govind Chandra, John Innes Centre, Norwich, UK
Funding
