Election Year: 2009
Primary Section: 44, Microbial Biology
Secondary Section: 22, Cellular and Developmental Biology
Membership Type: Foreign Associate
My research focuses on the molecular and cellular mechanisms underlying establishment and persistence of a bacterial infection. We use as a model Listeria monocytogenes, which is responsible for a food borne disease resulting in gastro-enteritis, meningitidis and materno-fetal infections. We study the bacterium and the host at the cell, tissue and animal level. Our research has led to the identification of a number of virulence factors including ActA, a protein responsible for intracellular actin-based motility and widely used to study actin polymerization. We have dissected the mechanisms allowing bacterial entry into cells, identified the two main bacterial proteins involved, i.e. internalin and InlB and discovered a species-specificity which has led us to generate the first transgenic mice expressing the human receptor. We then deciphered the contribution of internalin and InlB in the crossing of the intestinal and placental barriers. We showed that Listeria manipulate the host epigenetic information by controlling histone modifications through the action of listeriolysin O, a mechanism which down regulates immmunity genes. Using tiling arrays, we described two successive global transcriptional switches which occur during infection, a series of small RNAs -among which two are involved in virulence- and unexpected features such as long non-translated antisense transcripts. We discovered a new role for riboswitches as trans-acting small RNAs. Our research continues to focus on these different aspects and on post-translational modification induced by Listeria in infected cells.