|Bacteria-Cell Interactions - Inserm U604, INRA USC 2020|
|HEAD||Professeur Pascale Cossart / firstname.lastname@example.org|
|MEMBERS||AUBRY Camille, BAUDIER Martine, Dr BIERNE Hélène, Dr BONAZZI Matteo, Dr BALLESTRINO Damien, Dr DISSON Olivier, DORTET Laurent, Dr DUSSURGET Olivier, Gouin Edith, GOULARD Celine, Dr HAMON Mélanie, Dr KHELEF Nadia, Pr LECUIT Marc
Dr MOSTOWY Serge, NAHORI Marie-Anne, NIKITAS Giorgios, PERSONIC Nicolas, Dr PIZARRO-CERDA Javier, Dr RIBET David, Dr SABET Christophe, SESTO Nina, Dr THAM To Nam, Dr TOLEDO Alejandro, Dr VEIGA Esteban, VILLIERS Veronique
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 of course 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 cell biology approaches in particular in vivo imaging and relevant animal models in order to ultimately unravel at the molecular level the pathophysiology of human listeriosis. Our studies on Listeria which shed light on events occuring at the cell and tissue levels as well as at the level of the whole animal generate new concepts in both pathogenesis and cell biology.
New virulence factors : We concentrate our efforts on surface and secreted proteins. 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. This protein is under a post transcriptional regulation and is only expressed in animals after several days of infection. Its function is so far unknown.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. One of them which is not present in the non pathogenic species L. innocuadisplays a series of repeats and is involved in virulence by a so far unknown mechanisms.
The cell biology of the invasion process: We have extended our finding that the clathrin-mediated endocytosis machinery is used during Listeria entry, to several other zippering bacteria, highlighting a novel role for clathrin in internalization of large objects. Clathrin is also detected at the site of EPEC pedestal formation. We have discovered successive post-translational modifications of E-cadherin during infection highlighting novel similarities between Listeria entry and adherens junction formation ;
Genetic reprogrammation of the host cell through histone modifications and pathophysiology. We have demonstrated that Listeria induces a dramatic dephosphorylation of histone H3 and deacetylation of H4. This effect is mediated by the listerial toxin LLO prior to invasion and leads to the down regulation of key immunity genes. Similar effects are observed with toxins of the same family highlighting a common strategy used by intra and extracellular bacteria. We pursue our analysis of the crossing of host barriers using several models and in particular a new animal model, i.e. a knock-in humanized E-cadherin mouse line.
Keywords: Endocytosis, bacterial invasion, epigenetic regulation, actin, regulation
Gouin E, Egile C, Dehoux P, Villiers V, Adams J, Gertler F, Li R, Cossart P. (2004). The RickA protein of Rickettsia conorii activates the Arp2/3 complex. Nature, 427 : 457-461.
Sousa S, Cabanes D, Colland F, Lecuit M, Legrain P, Cossart P. (2005) ARHGAP10 is necessary for -catenin recruitment at adherens junctions and for Listeria invasion. Nat. Cell Biol., 7 : 954-960.
Veiga E. and Cossart P. (2005) Listeria hijacks the clathrin-dependent endocytic machinery to invade mammalian cells. Nat. Cell. Biol., 7 : 894-900.
Hamon MA, Batsché E, Régnault B, Tham TN, Seveau S, Muchardt C, Cossart P. (2007) Histone modifications induced by a family of bacterial toxins. Proc Natl Acad SciU S A., 104: 13467-72. Erratum in: Proc Natl Acad SciU S A., 104: 17555.
Boneca IG, Dussurget O, Cabanes D, Nahori MA, Sousa S, Lecuit M, Psylinakis E, Bouriotis V, Hugot JP, Giovannini M, Coyle A, Bertin J, Namane A, Rousselle JC, Cayet N, Prévost MC, Balloy V, Chignard M, Philpott DJ, Cossart P, Girardin SE. (2007).A critical role for peptidoglycan N-deacetylation in Listeria evasion from the host innate immune system. Proc Natl Acad SciU S A., 104: 997-1002.
Activity Reports 2007 - Institut Pasteur
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