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Alice Lebreton

Bacterial Infection and RNA Destiny

BIRD team, 2021

The onset cell infection by a bacterial pathogen such as Listeria monocytogenes constitutes a remarkable example of dynamic phenomena in biology, where both the host cell and pathogen respond to each-other in a series of attacks and responses referred-to as a molecular crosstalk. Our research is dedicated to the study of this dynamics across time and space.

FAST highlights an unexpected intravacuolar lifestyle for Listeria

Discover the trans-disciplinary collaboration between microbiology, chemical biology and biophysics that gave birth to our latest work (Peron-Cane et al., PLoS Pathogens 2020) in this report.

Extended model of Listeria monocytogenes intracellular life cycle in human epithelial cells. Illustration © Ève Barlier, 2020.

This project is ongoing: we now wish to understand how this new niche is formed, maintained, and its consequences. Feel free to contact us in case you feel tempted by joining us. We’re currently hiring a post-doc.

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 to test hypotheses that may later be extended to other bacterial infections. We aim at providing elements of answers to the following questions:

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


Our studies combine molecular biology, functional genomics, cellular microbiology and chemical biology approaches, with the aim of providing 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. We are also gaining insight into the intracellular lives of Listeria and the dynamics of its secreted virulence factors in real-time microscopy.

Peron-Cane C, Fernandez J-C, Leblanc J, Wingertsmann L, Gautier A, Desprat N and Lebreton A. Fluorescent secreted bacterial effectors reveal active intravacuolar proliferation of Listeria monocytogenes in epithelial cells. PLoS Pathog (2020) 16(10):e1009001.

Besic V, Habibolahi F*, Noël B*, Rupp S, Genovesio A and Lebreton A. Coordination of transcriptional and translational regulations in human cells infected by Listeria monocytogenes. RNA Biol (2020) 17(10):1492-1507.

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

 corresponding authors; * equal contribution




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