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New concepts in host-pathogen interactions: lessons from Listeria

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Pathogens have long co-evolved with their host and have devised elegant and efficient strategies to exploit to their own profit molecules or mechanisms critical for the host. The study of these strategies has led not only to the discovery of amazing tricks used by pathogens during infection but also to that of unsuspected mechanisms normally used by the cell. Pathogens thus appear as very powerful tools to address critical issues in Cell Biology. We will illustrate this duality by presenting several aspects of the infection by Listeria monocytogenes, a food borne bacterium which is able to invade mammalian cells and spread directly form cell to cell. Other bacteria will also be discussed. We will first show how Listeria orchestrates its entry into cells, and will present the discovery of an unsuspected role of clathrin in the early cytoskeleton rearrangments leading to internalization. We will also discuss how septins are increasingly recognized as important components of the cytoskeleton and as such also control the Listeria entry process. Interestingly, septins are able to entrap some cytosolic bacteria able to move from cell to cell such as Shigella but not Listeria in a process tighly coupled to autophagy and which limits their actin-based dissemination. Finally, we recently discovered that Listeria can reprogram its host by injecting into the infected cell a protein that interact with a previously unknown heterochromatinisation factor and prevent its action raising the possibility that chromatin marks could remain after infection. A new field of investigation, i.e. chromatin remodeling by pathogens and a new discipline « pathoepigenetics » are emerging.

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