Guillaume Duménil
INSERM U970 PARCC
56 rue Leblanc, 75015 Paris
 
Research area of the Unit
Septic shocks and meningitis caused by bacterial infection of the vasculature are major public health problems. A central hypothesis of our group is that these diseases should be considered as pathologies of the vascular system. Our goal is two fold: (i) to determine the impact of such infections on the vasculature at the molecular and cellular level; (ii) identify innovative strategies to block the deleterious effects of infection on the vascular system. Our main focus has been the Gram-negative bacterium Neisseria meningitidis. This pathogenic bacterium presents the typical features of infection of the bloodstream, proliferation in the vessel lumen, vessel damage causing leakage, exit of the pathogen from the lumen to cerebrospinal fluid. Another argument to use this bacterium as a model system is that, experimentally, N. meningitidis can be easily manipulated genetically.
Contribution to the programme
A large number of emerging infectious agents reach the blood during infection, in most cases this step is a sign of extreme severity of the disease. Colonization of the blood can have different types of pathological consequences for the vascular system.
- Vascular leak: In this case infection affects the junctions between the endothelial cells leading to hemorrhagic syndromes
- Septic shock: The most severe consequence of colonization of the blood by a variety of Gram negative or positive bacteria. Infection triggers an intense and deregulated inflammation.
- Dissemination to other organs: In other instances, blood colonization can be the port of entry to other organs such as the brain infection, leading to further complications and sequelae.
- Endocarditis: Heart valves are the site of infection and can be progressively destroyed by pathogens leading to heart failure.
Our contribution to the program is to provide our knowledge and tools to study the molecular and cellular basis underlying these pathological effects, both on the side of the microorganism and on the host.
References over the past 5 years
1. Melican K, Dumenil G (2012) Vascular colonization by Neisseria meningitidis. Curr Opin Microbiol 15: 50-56.
2. Chamot-Rooke J, Mikaty G, Malosse C, Soyer M, Dumont A, Gault J, Imhaus AF, Martin P, Trellet M, Clary G, Chafey P, Camoin L, Nilges M, Nassif X, Dumenil G (2011) Posttranslational modification of pili upon cell contact triggers N. meningitidis dissemination. Science 331: 778-782.
3. Soyer M, Dumenil G (2011) Introducing Shear Stress in the Study of Bacterial Adhesion. J Vis Exp.
4. Coureuil M, Mikaty G, Miller F, Lecuyer H, Bernard C, Bourdoulous S, Dumenil G, Mege RM, Weksler BB, Romero IA, Couraud PO, Nassif X (2009) Meningococcal type IV pili recruit the polarity complex to cross the brain endothelium. Science 325: 83-87.
5. Mikaty G, Soyer M, Mairey E, Henry N, Dyer D, Forest KT, Morand P, Guadagnini S, Prevost MC, Nassif X, Dumenil G (2009) Extracellular bacterial pathogen induces host cell surface reorganization to resist shear stress. PLoS Pathog 5: e1000314.
6. Chamot-Rooke J, Rousseau B, Lanternier F, Mikaty G, Mairey E, Malosse C, Bouchoux G, Pelicic V, Camoin L, Nassif X, Dumenil G (2007) Alternative Neisseria spp. type IV pilin glycosylation with a glyceramido acetamido trideoxyhexose residue. Proc Natl Acad Sci U S A 104: 14783-14788.
7. Mairey E, Genovesio A, Donnadieu E, Bernard C, Jaubert F, Pinard E, Seylaz J, Olivo-Marin JC, Nassif X, Dumenil G (2006) Cerebral microcirculation shear stress levels determine Neisseria meningitidis attachment sites along the blood-brain barrier. J Exp Med 203: 1939-1950.