Institut de Biologie StructuraleGrenoble / France

Bacterial Pathogenesis and Cellular Responses Group

Group leader : Ina Attree

IBS-PB&RC
Bat C3, CEA-Grenoble
17 avenue des Martyrs
38 054 Grenoble cedex 9
Tel. : 04 38 78 22 19
Fax : 04 38 78 44 99

General Presentation

The focus of Bacterial Pathogenesis and Cellular Responses (PB&RC) Team is basic research aiming at deciphering the virulence mechanisms, as well as strategies the bacterial pathogens use to resist antimicrobials (antibiotics, immune system components) and promote infections. The team is recognized for its expertise on bacterial virulence using Pseudomonas aeruginosa as a model. We study host-pathogen interplay by integrated approaches from genetics, biochemistry, cellular microbiology and genome-wide genetic screens (CRISPR-Cas and Tn-Seq, RNA-Seq). The team is positioned at the interface of translational research with possible applications in clinics.
Our model is P. aeruginosa, recognized as a major human opportunistic pathogen ; it provokes acute and chronic infections, notably in immunocompromised patients or associated with other pathologies, such as cystic fibrosis, or patients under ventilation in Intensive Care Units. Therefore, P. aeruginosa is considered as a nosocomial pathogen. The main problem of treating P. aeruginosa infections is its antibiotic resistance and its amazing adaptation capacities, which results in synthesis of numerous toxic products that allow host invasion, colonization and spread. P. aeruginosa possesses a number of secretion machineries that permits the transfer of bacterial proteins from the cytoplasm toward the extracellular milieu, or even the direct translocation within the host cell. These secretion systems confer to P. aeruginosa the virulence capacity, which may be more or less important, depending on expression levels or combination of toxins one given strain is employing. More specifically, our goal is to understand the the regulation of expression of its virulence factors, mechanisms the pathogen employs to breach epithelial and endothelial barriers and ways the bacteria resist to immune system leading to acute and chronic infections. To achieve this goal, we have developed a pipeline that allows us to study different bacterial proteins/toxins by integrated approaches and to assign their role(s) in pathogenesis using cellular and simple animal models.

Members

Permanent

  • Sandrine Boisset, Ph.D.(MCU-PH, PharmD)
  • Stéphanie Bouillot, (CEA Advanced Technician)
  • Yvan Caspar, Ph.D (Hospital-University Practicien, PharmD)
  • François Cretin, Ph.D (Associated Professor UGA)
  • Sylvie Elsen, Ph.D (CNRS Researcher, CR) HDR
  • Eric Faudry, Ph.D (CEA Research Engineer, CR) HDR
  • Viviana Job, Ph.D (CEA Research Engineer)
  • Antoine Maillard, Ph.D (CEA Research Engineer, CR), HDR
  • Michel Ragno, (CNRS Technician)
  • Mylène Robert-Genthon, (CNRS Advanced Technician)

PhD

  • Aimé Barwa (Pharmaceutical Innovation and Research Intern)
  • Manon Janet-Maitre
  • Léa Ponderand (Hospital Practitioner)
  • Adèle Renier
  • Victor Simon

Trainee

  • Arthur Deves, (Master 2)

Alumin

  • Emily Rey, (Master 2)
  • Faustine Toro, (BTS alternance)
  • Mélissa Feugas, (IUT)
  • Beatrice Cesana, (Master 1)
  • Morgane Roger, (Master 1)
  • Adam Valin, (Phelma)
  • Fabien Chenavier, (L3)

Research topics

The Bacterial Pathogenesis and Cellular Responses (PB&RC) Team is recognized for its expertise on bacterial virulence using Pseudomonas aeruginosa as a model. The focus of the team is a basic research aiming at deciphering the virulence mechanisms, as well as strategies the pathogens use to resist antimicrobials (antibiotics, immune system components) and promote infections. We study host-pathogen interplay by integrated approaches from genetics, biochemistry, cellular microbiology and genome-wide genetic screens (CRISPR-Cas and Tn-Seq, RNA-Seq). The team is positioned at the interface of translational research with possible applications in clinics.

Keywords

Pseudomonas aeruginosa, toxin, cystic fibrosis, T3SS, T6SS, translocon, needle, injectisome, host-pathogen interaction, interactome, chemogenomics, regulation, signaling

Specific techniques

- Bacterial genetics (engineering of KO mutants),
- Cellular bacteriology,
- Genome-wide screens (CRISPR-Cas and Transposon),
- NGS (Tn-Seq, WGS, DAP-Seq, CHIP-Seq, RNA-Seq...).
- Microscopy (Fluorescence microscopy, IF, 3D video, confocal spinning-disk microscopy, automated microscopy and image analysis)
- Host pathogen interaction (infection models eg : Galleria mellonella, macrophages, epithelial cells and human blood)
- Intra-bacterial competition assay (E.coli, Pseudomonas sp, Acinetobacter, Bacillus sp…)
- FACS (cytokines measurements, detection and quantification of surface proteins, T3SS toxins injection test using beta-lactamase conjugation, sorting of cells and bacteria),
- Protein expression and purification (in E. coli and P.aeruginosa),
- Protein-protein and protein-lipid interactions, lipid raft purification.

Collaborations

  • CHU Grenoble,
  • Harvard Medical School, Boston (Steve Lory),
  • IDMIT institute (Fontenay-aux-Roses) (Philippe Huber)
  • University of Lyon, Microbiologie Adaptation et Pathogénie (Erwan Gueguen)
  • Institut Pasteur, Paris (Carmen Buchrieser)
  • Gen&Chem team (Marie-Odile Fauvarque) : Pseudomonas/Drosophila interaction and CMBA platform (chemolibraries and phenotypic High Content microscopy screening)
  • EDyP-Service (Yohann Couté) : Mass spectrometry analyses

Key publications

Vincent Deruelle, Stéphanie Bouillot, Viviana Job, Emmanuel Taillebourg, Marie-Odile Fauvarque, Ina Attrée and Philippe Huber (2021) The bacterial toxin ExoU requires a host trafficking chaperone for transportation and to induce necrosis. Nature Communications https://doi.org/10.1038/s41467-021-24337-9

Alexandre Martins, Carlos Contreras-Martel, Manon Janet-Maitre, Mayara M. Miyachiro, Leandro F. Estrozi, Daniel Maragno Trindade, Caíque C. Malospirito, Fernanda Rodrigues-Costa,Lionel Imbert, Viviana Job, Guy Schoehn, Ina Attrée and Andréa Dessen. (2021) Self-association of MreC as a regulatory signal in bacterial cell wall elongation. Nature Communications https://doi.org/10.1038/s41467-021-22957-9

Pont S, Fraikin N, Caspar Y, Van Melderen L, Attrée*, I. and Cretin*, F. (2020) Bacterial behavior in human blood reveals presence of complement evaders with persister-like features. 16(12):e1008893. PLoS Pathogens. doi : 10.1371/journal.ppat.1008893.

Trouillon J, Sentausa E, Ragno M, Robert-Genthon M, Lory S, Attrée I, Elsen S. (2020). Species-specific recruitment of transcription factors dictates toxin expression Nucleic Acids Res., 48(5):2388-2400. doi : 10.1093/nar/gkz1232

Ngo TD, Plé S, Thomas A, Barette C, Fortuné A, Bouzidi Y, Fauvarque MO, Pereira de Freitas R, Francisco Hilário F, Attrée I, Wong YS, Faudry E. (2019) Chimeric Protein-Protein Interface Inhibitors Allow Efficient Inhibition of Type III Secretion Machinery and Pseudomonas aeruginosa Virulence. ACS Infect Dis. 8 ;5(11):1843-1854. doi : 10.1021/acsinfecdis.9b00154

Reboud E, Bouillot S, Patot S, Béganton B, Attrée I and Huber P. (2017). Pseudomonas aeruginosa ExlA and Serratia marcescens ShlA trigger cadherin cleavage by promoting calcium influx and ADAM10 activation. 23 ;13(8):e1006579. PLoS Pathogens. doi : 10.1371/journal.ppat.1006579.

A list of all publications can be found here (link to be confirmed).