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Paris, March 11, 2011

Discovery of a new bacterial strategy to control immunity

Researchers at the Institut Pasteur, INRA, Inserm and the CNRS have just identified a mechanism that enables the pathogenic bacterium Listeria monocytogenes to reprogram expression of the genes in the host cell it infects to its advantage. L. monocytogenes secretes a protein that can penetrate the cell nucleus and thus take control of the genes in the host’s immune system. This research was published in the journal Science.


During infection, pathogenic bacteria have to overcome the immune defenses of the infected host organism in order to take up residence there. Up until now we knew that the host’s immune system was controlled by manipulation of the cell signals that activate the cells of the immune system. But now a study carried out on Listeria monocytogenes, the bacterium that causes listeria infections in humans, has shown for the first time that pathogenic bacteria can act directly within the host cell’s nucleus to reprogram some genes regulated by interferons that activate the immune system (1). The research was carried out by Hélène Bierne of the Bacteria-Cell Interactions Unit (Institut Pasteur, Inserm Unit 604, INRA USC2020), headed by Pascale Cossart, and in collaboration with other teams from the Institut Pasteur, the CNRS (Gif-sur-Yvette, Paris Diderot - Paris 7 University and Grenoble) and the Institute for Molecular and Cell Biology in Porto (Portugal).


 This research is coupled to a study carried out by the same team in 2009, which identified a complex capable of blocking gene expression by compacting DNA (2). The researchers identified a small bacterial protein known as LntA that can overcome this block by binding directly to the complex, thereby causing the compacted DNA to open and providing access to the genes.

We still do not know how and at what point the bacterium activates secretion of this LntA factor, but its expression is crucial to the process of infection by Listeria, enabling it to activate or inhibit the host’s immune system at will.

This study points to the role of epigenetic regulation – changes in the expression of genes that occur without any change to the DNA sequence – ininfection by L. monocytogenes. If this discovery is confirmed for other pathogens too, it could provide valuable clues to further our understanding of infectious and immune diseases, and eventually help us to combat them more effectively.

This research has received funding from the European Community (ERANET PathoGenomics and ERC programs).

Photo caption: LntA bacterial protein (green-yellow) in the nucleus of two human cells infected by Listeria (purple-blue). © Institut Pasteur

Source

 

(1) A Bacterial Protein Targets the BAHD1 Chromatin Complex to Stimulate Type III Interferon Response, Science 11 March 2011: 1319-1321.
 
Alice Lebreton (1,2,3), Goran Lakisic (4), Viviana Job (5), Lauriane Fritsch (6), To Nam Tham (1,2,3), Ana Camejo (7), Pierre-Jean Matteï (5), Béatrice Regnault (8), Marie-Anne Nahori (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-75015 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, Paris-Diderot / Paris 7 University, Paris, F-75013 France.
(7) Institute for Molecular and Cell Biology, Porto, Portugal.
(8) Institut Pasteur, Genopole, 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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