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Alice Lebreton

Bacterial Infection and RNA Destiny

BIRD team, 2016


The food-borne pathogen Listeria monocytogenes is the etiological agent of listeriosis, an opportunistic disease with serious outcomes in the elderly, in immunocompromised individuals, foetuses or new-borns. L. monocytogenes can cross the host intestinal, foeto-placental and blood brain barriers, allowing its dissemination throughout the organism. This bacterium can enter and multiply in the cytosol of most human cell types and spread to neighbouring cells, using an arsenal of virulence factors that target diverse cellular components and subsequently hijack various eukaryotic cell functions.

One major aspect of the host-bacterium dialogue during infection is the thorough remodelling of both gene expression patterns. The combination of these bacterial and cellular activities conditions bacterial physiology, cell survival, tissue immune responses, and finally shapes the pathological outcome of the infection. In-depth understanding of the various regulatory levels at play, and of their dynamics, is of major importance to apprehend how host cell functions are affected by infection.

Objectives


Our team explores the post-transcriptional mechanisms affecting host gene expression during infection by Listeria monocytogenes. We use this model intracellular bacterium as a tool for a proof-of-concept, which could be extended to other bacterial infections. Our projects aim at providing elements of answers to the following questions:

  • What is the impact of infection on cellular RNA stability?
  • Is translation affected by infection?
  • What are the bacterial or host molecular mechanisms involved in these processes?
  • What are the pathological consequences?


Our studies combine RNA-seq based technologies and their integrative computational biology analysis with more classical approaches in cellular microbiology, molecular biology and biochemistry. We believe they will generate a better understanding of the mutual requirements for bacteria-host niche adaptation, lead to the characterization of new virulence factors, and allow us to explore of eukaryotic translational control pathways in the light of infection.

Lebreton A and Cossart P. RNA- and protein-mediated control of Listeria monocytogenes virulence gene expression. RNA biol. (2017) 14(5):460-70 (Review).

Duval M, Cossart P and Lebreton A. Mammalian microRNAs and long noncoding RNAs in the host-bacterial pathogen crosstalk. Semin Cell Dev Biol. (2017) 65:11-19 (Review).

Lebreton A, Stavru F and Cossart P. Organelle targeting during bacterial infection: Insights from Listeria. Trends Cell Biol. (2015) 5(6):330-338 (Review).

Cossart P and Lebreton A. A trip in the “New Microbiology” with the bacterial pathogen Listeria monocytogenes. FEBS Letters (2014) 588(15):2437-45 (Review).

Lebreton A, Lakisic G, Job V, Fritsch L, Tham TN, Camejo A, Matteï P-J, Regnault B, Nahori M-A, Cabanes D, Gautreau A, Ait-Si-Ali S, Dessen A, Cossart P and Bierne H. A bacterial protein targets the BAHD1 chromatin complex to stimulate type III interferon response. Science (2011) 331(6022):1319-21.

Lebreton A*, Rafal T*, Dziembowski A and Séraphin B. Endonucleolytic RNA cleavage by a eukaryotic exosome. Nature (2008) 456(7224):993-7.

 co-corresponding authors; * equal contribution




Intracellular bacterial infection reprograms gene expression.
Intracellular bacterial infection reprograms gene expression.