Research Interests - Alice Lebreton-Mansuy

Ph.D. - INRA research Scientist

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Pubmed bibliography

I am working in the group “Nuclear Signaling, Epigenetics and Infection” nucleated by Hélène Bierne. Since I joined the lab in 2008, my research focuses on deciphering the molecular mechanisms by which Listeria monocytogenes modulates host type-III interferon (IFN-λ) response by subverting chromatin silencing.

LntA, a virulence factor secreted by Listeria and targeting the host cell nucleus

LntA alleviates BAHD1-mediated silencing of ISGs

 

Hélène Bierne initiated the characterization of a new virulence factor of Listeria monocytogenes, LntA, revealed by post-genomic studies. Bacteria secrete this small, basic protein, during the infection process. It is then targeted to the nucleus of host cells, where it interacts with a chromatin protein, BAHD1, and regulates the transcription of host genes.

We have shown that, when Listeria monocytogenes infects epithelial cells, it can induce the type III interferon pathway, leading to the activation of a set of immunity genes, Interferon Stimulated Genes (ISGs). However, the infection also triggers the repression of these genes by the BAHD1 chromatin-silencing complex.

When intracellular bacteria secrete LntA, it enters the nucleus of infected cells and alleviates the action of the BAHD1 complex; thereby, LntA activates ISGs. These mechanisms enable Listeria to either stimulate or suppress the type-III interferon pathway along the infectious process.

(Lebreton et al., Science, 2011)

lntA, a tightly controlled virulence gene

During our previous works, we have we have observed that the lntA gene expression was tightly locked in most conditions, which probably prevents inappropriate activation of host defences and subsequent bacterial clearance.

I am now trying to unravel the lntA regulation mechanisms, and to define precisely when and where lntA expression is turned on during the infectious process. This should provide a better understanding of the reasons why Listeria needs to activate IFN-λ response for efficient listeriosis.

In parallel, I keep on characterizing in details the mechanisms of LntA-mediated regulation of ISGs, by studying the pattern of chromatin modifications and its consequences on the outcome of infection. This is necessarily intimately linked to in-depth studies of LntA human partner, BAHD1, both in vivo and in vitro. Additionally, in collaboration with Viviana Job and Andréa Dessen at the Institut de Biologie Structurale (Grenoble), who solved the structure of LntA by crystallography, I am deciphering the molecular determinants required for a functional LntA-BAHD1 interaction.


Updated on 12/05/2014

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Lab address

Unité Interactions Bactéries-Cellules

INSERM U604 INRA USC2020
Institut Pasteur
25, Rue du Docteur Roux
75724 Paris Cedex 15 FRANCE

 

Phone: + 33 (1) 45 68 88 41

Secretary: + 33 (1) 40 61 30 32

Fax: + 33 (1) 45 68 87 06

 

Our laboratory is located on the ground floor at the 53C entrance of the Roux Building (25, rue du Docteur Roux)

The metro stations Pasteur (line 6) and Volontaires (line 12) are within a 5 min walking distance from the Pasteur Institute.

The bus stop Pasteur (bus 95, towards Porte de Vanves) is located next to the Pasteur Institute main entrance.

For more information: Pasteur Institute Access and Paris Metro/Bus/Tram

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