Integrative Biology of Emerging Infectious Diseases (IBEID) / Principal investigators
Bacteria Cell Interactions Unit
Institut Pasteur 25-28 rue du docteur Roux, 75015 Paris
Research area of the Unit
Our Unit investigates the molecular and cellular basis of the infection by Listeria monocytogenes, a model pathogen for the study of the intracellular parasitism. L. monocytogenes is responsible for severe foodborne infections. This bacterium is characterized by its ability to cross three host barriers -the intestinal, blood-brain or feto-placental barriers- and to invade several cell types in which it multiplies. L. monocytogenes moves in the cytosol of infected cells and spreads from cell to cell using an original propelling process; i.e. cell actin polymerization at one pole of the bacteria.
Our present activity focuses on: 1) the identification and characterization of new non-coding RNAs involved in virulence, as well as new RNA-mediated regulations; 2) the investigation of new molecular pathways involved in bacterial entry into host cells and cell-to-cell spread; 3) organelle dynamics during infection; 4) the systematic analysis of post-translational modifications of host molecules during infection, in particular SUMOylation; 5) chromatin remodeling upon infection; 6) the characterization of new bacterial virulence factors identified by post-genomic approaches or by their effect on cellular responses; and 7) in-depth understanding of the intestinal phase of the L. monocytogenes infection by analyzing the impact of commensals on L. monocytogenes growth and the bacterial effect on the intestinal tissue.
In many of these research themes, we try to generalize our findings to other bacterial models.
Contribution to the programme
Basic microbial physiology / novel aspects of microbiology
Taking as a primary model the bacterium Listeria monocytogenes, the group will invest a significant effort in the exploration of novel regulatory mechanisms in bacteria. Using in particular its custom made tiling arrays coupled to deep sequencing of RNA samples, the group will investigate the role of small regulatory RNAs in virulence. The role of long non-coding transcripts will also be studied.
Post-translational modifications during infection
The group will investigate host post-translational modifications during infection of cells with pathogen or during cell contacts with commensals/ probiotics. This systematic programme will absolutely require a significant scaling up of the existing proteomic facilities as SILAC will have to be routinely used.
Microbiota in health and disease
The group will investigate in collaboration with M. Lecuit the role of probiotics/ commensals on the infection by Listeria using the germ free mouse line. Both the mouse (pathophysiology and microRNAs) and the bacterial partners will be analyzed.
References over the past 5 years
1. Wurtzel, O., N. Sesto, J.-R. Mellin, I. Karunker, S. Edelheit, C. Becavin, C. Archambaud, P. Cossart and R. Sorek (2012). Comparative transcriptomics of pathogenic and non-pathogenic Listeria species. Mol Syst Biol, 8:583
2. Lebreton A., G.Lakisic, V. Job, L. Fritsch, T.-N.Tham, A. Camejo, P.-J. Matteï, B. Regnault, M.-A. Nahori, D. Cabanes, A. Gautreau, S. Ait-Si-Al, A. Dessen, P. Cossart and H. Bierne (2011). A bacterial protein targets the BAHD1 chromatin complex to stimulate Type III interferon response. Science, 331:1319-21
3. Stavru F., F. Bouillaud, A. Sartori, D. Ricquier, and P. Cossart (2011). Listeria monocytogenes transiently alters mitochondrial dynamics during infection. Proc Natl Acad Sci USA, 108:3612-7
4. Gouin E., M. Adib-Conquy, D. Balestrino, M.-A. Nahori, V. Villiers, F. Colland, S. Dramsi, O. Dussurget and P. Cossart (2010). The Listeria monocytogenes InlC protein interferes with innate immune responses by targeting the IκB kinase α. Proc Natl Acad Sci USA, 107:17333-8
5. Ribet, D., M. Hamon, E. Gouin, M.A. Nahori, F. Impens, H. Neyret-Kahn, K. Gevaert, J. Vandekerckhove, A. Dejean, and P. Cossart, (2010). Listeria monocytogenes impairs SUMOylation for efficient infection. Nature, 464:1192-1195
6. Toledo-Arana, A., O. Dussurget, G. Nikitas, N. Sesto, H. Guet-Revillet, D. Balestrino, E. Loh, J. Gripenland, T. Tiensuu, K. Vaitkevicius, et al. (2009). The Listeria transcriptional landscape from saprophytism to virulence. Nature, 459:950-956
7. Hamon, M.A., E. Batsche, B. Regnault, T.N. Tham, S. Seveau, C. Muchardt, and P . Cossart, (2007). Histone modifications induced by a family of bacterial toxins. Proc Natl Acad Sci USA, 104:13467-13472