Bacteria-Cell Interactions - INSERM U604, INRA USC2020  


  HEADProf. COSSART Pascale / pcossart@pasteur.fr
  MEMBERSDr BIERNE Hélène / Dr BONAZZI Matteo / Dr BALLESTRINO Damien / Dr DISSON Olivier
DORTET Laurent / Dr DUSSURGET Olivier / GOUIN Edith / GOULARD Céline / Dr HAMON Melanie
Dr KHELEF Nadia / Prof. LECUIT Marc / Dr MOSTOWY Serge / NAHORI Marie-Anne
NIKITAS Georgios / PERSONIC Nicolas / Dr PIZARRO-CERDA Javier / SABET Christophe
Dr THAM To Nam / Dr TOLEDO Alejandro / Dr VEIGA Esteban


  Annual Report

Our research focuses on the analysis of the infectious process by intracellular bacteria, using as a model system Listeria monocytogenes. Our goal is to identify bacterial and cellular components - and the mechanisms in which they are involved - which are critical for establishment and persistence of a Listeria infection. We use multidisciplinary approaches ranging from post-genomics to sophisticated cell biology approaches and in vivo imaging in relevant animal models to ultimately unravel at the molecular level the pathophysiology of human listeriosis. Our studies shed light on events at the cell and tissue levels as well as at the level of the whole animal. They contribute to general concepts in both pathogenesis and cell biology.

New virulence factors : We concentrate our efforts on surface and secreted proteins. We have shown that the unique superoxide dismutase (SOD), is secreted in the host cell and inactivated by a host kinase, highlighting a novel host defense mechanism which may take place during infection with other pathogens. We have identified a novel protein of the internalin family, InlJ whose role in virulence is clearly established but which does not play any role during infection of cultured cells. We investigate the role of some intriguing features of this molecule. We have also identified a secreted protein which goes to the cell nucleus. Experiments indicate a role for this protein in heterochromatin formation and in an epigenetic control of gene expression during infection. Finally, we have identified a peptidoglycan (PG) deacetylase whose absence leads to a high sensitivity to lyzozyme and a robust inflammatory response, highlighting one key strategy, i.e. PG deacetylation, used by gram positive bacteria to escape host defences.

Small RNAs: We have identified nine novel small RNAs. We generated a program to predict targets and validated targets for three of them. Our goal is to identify RNAs controlling virulence.

The cell biology of the invasion process and of the intracellular life: We have extended our finding that the clathrin-mediated endocytosis machinery is used during Listeria entry, to several other bacteria.

We investigate the role of components initially detected on isolated internalization vacuoles, e.g. PI 4-kinase and septins. Both are critical for entry. Septins control bacterial escape from the vacuole.

Host response to infection and pathophysiology: We study the host response either at the cell level using purified proteins or bacteria or at the tissue level after oral infection. We discovered that one of the major factors regulating the host cell reprogrammation is not the entry into the cell but the secretion of a toxin, the potent listeriolysin O. We are achieving the generation of a new animal model, i.e. a knock-in humanized E-cadherin mouse line.

cossart.jpg

Figure : Recrutement de la clathrine autour de Listeria pendant l’invasion (rouge clathrine endogène ; vert : Listeria intracellulaires ; bleu Listeria extracellulaires)

Figure: Clathrin recruitment around Listeria during invasion (red: endogenous clathrin: green intracellular bacteria, blue extracellular bacteria).



  Publications

Publications 2006 of the unit on Pasteur's references database




Activity Reports 2006 - Institut Pasteur
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