Published Tuesday, January 25, 2011
Researchers at the Pasteur Institute, INRA, INSERM and CNRS have identified a mechanism that allows pathogenic bacteria Listeria monocytogenes to his advantage to reprogram the gene expression of the cell it infects. L. monocytogenes secretes a protein that can penetrate the nucleus of cells to take control of immune system genes of the host. This work has been published on the website of the journal Science January 20, 2011.
During infection, pathogenic bacteria must outwit the immune system of the infected host to reach a sustainable manner in their body. We knew previously that the control system of the host immune passed through the manipulation of cellular signals responsible for the activation of immune cells. A study in Listeria monocytogenes, the bacterium responsible for human listeriosis, has first to show that pathogenic bacteria can act directly in the nucleus of the host cell to their advantage to reprogram the genes under the control of interferons, intended to activate the immune system (1). The study was led by Helene Bierne within the unit cell-bacteria interactions (Institut Pasteur, Inserm Unit 604, INRA USC2020) directed by Pascale Cossart, in collaboration with other teams from the Institut Pasteur, CNRS (Gif-sur-Yvette, Université Paris Diderot - Paris 7 and Grenoble) and IBMC (Porto).
This work is in line with a study by the same team in 2009. This allowed the identification of a complex capable of locking the expression of genes in compacting the DNA (2). Here, researchers have identified a small bacterial protein, called LNTA able to blow the lock by binding directly to the complex, which causes the opening of the compacted DNA and thus access genes.
It is still unclear how and when the bacteria determines the production of this factor LNTA, but its expression is fundamental to the success of infection with Listeria, which can activate it through or suppress at will the host immunity. These studies suggest the role of epigenetic regulation - changes in gene expression that occur without altering the DNA sequence - in infection with L. monocytogenes. This discovery, if it were applied to other pathogens, provide valuable information to better understand and, ultimately, to better fight against the infectious disease and immunity.This study received financial support including the European Community (ERANET PathoGenoMics programs and ERC).
(1) A Bacterial Protein Targets The BAHD1 Chromatin Complex to Stimulate Type III Interferon Response, Science Online, 20 January 2011
Alice Lebreton (1,2,3), Goran Lakisic (4), Viviana Job (5 ), Lauriane Fritsch (6), To Nam Tham (1,2,3), Ana Camejo (7), Jean Pierre Mattei (5), Béatrice Regnault (8), Marie-Anne Nahor (1,2,3) Didier Cabanes (7), Alexis Gautreau (4), Slimane Ait-Si-Ali (6), Andréa Dessen (5), Pascale Cossart (1,2,3) and Hélène Bierne (1.2, 3)
(1) Institut Pasteur, Bacteria Cell Interactions Unit, Paris, F -75,015 France;
(2) Inserm, U604, Paris, F-75015 France;
(3) INRA, USC2020, Paris F-75015 France.
(4) CNRS UPR3082, Laboratory of Enzymology and Structural Biochemistry, Gif-sur-Yvette, F-91198 France.
(5) Institute of Structural Biology, Bacterial Pathogenesis Group, UMR 5075 (CNRS / CEA / UJF), Grenoble, France.
(6) CNRS UMR7216, Université Paris-Diderot / Paris 7, Paris, F-75013 France.
(7) Institute for Molecular and Cell Biology, Porto, Portugal.
(8) Institut Pasteur, Génopole, Paris, F-75015 France.(2) « Human BAHD1 promotes heterochromatic gene silencing », PNAS, 2009, vol. 106 _ no. 33 pp. 13826-13831.
Hélène Bierne, To Nam Tham, Eric Batsche, Anne Dumay, Morwenna Leguillou, Sophie Kernéis-Golsteyn, Béatrice Regnault, Jacob-S Seeler, Christian Muchardt, Jean Feunteun and Pascale Cossart.
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