Institut de Biologie de l'École Normale Supérieure ENS . CNRS UMR8197 . Inserm U1024 Directeur : Pierre Paoletti

Bacterial infection, response & dynamics

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.

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 bacterial-host interplay 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. The activity of the secreted virulence factors secreted by Listeria and interfering with host functions, as well as the cellular stress caused by bacterial assaults, contribute to shaping these regulations and their outcomes.

Objectives

Our team studies the molecular crosstalk that takes place during the infection of human epithelial cells by Listeria monocytogenes across time and space. We use this model intracellular bacterium to test hypotheses that may later be extended to other bacterial infections. Our research follows two main tracks:

• Exploring the dynamics of the host gene expression in response to infection, with a special focus on the post-transcriptional regulation mechanisms that control this response, the signaling pathways that induce them, and their functional consequences.
• Investigating the recently-uncovered heterogeneity of Listeria lifestyles in distinct subcellular niches, the host and bacterial mechanisms that allow them, and their impact on infection.

  
  Our research combines 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, leading to the characterization of new virulence factors, and allowing us to explore 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.