Guy CORNELIS

Présentation

In 1984, Guy was appointed as Lecturer at the Univ. of Louvain where he initiated studies on the pathogenesis of Yersinia enterocolitica, a common food-borne agent of benign gastroenteritis which belongs to the same bacterial genus as Yersinia pestis, the agent of plague. These studies led to the discovery of type III secretion (T3S), a concept that was pioneered in parallel by H. Wolf-Watz in Umea, Sweden, and presented in (Cornelis and Wolf-Watz, Mol. Microbiol., 1997, 23: 861-67). T3S is a mechanism by which many Gram- bacteria inject "effector" proteins into the cytosol of animal, plant or insect cells. The effectors disarm the target cell by sabotaging the cellular signaling network. The T3S apparatus, called injectisome, is a complex nanosyringe made of more than 25 different proteins. It consists of a transmembrane basal body and a ca 60-nm long needle protruding from the surface. Yersinia utilize such a system to inject anti-phagocytic and anti-inflammatory effector proteins (called Yops) into cells of the host immune system. The milestones of this research in Guy's laboratory are a) the initial observation that Yops are secreted without the removal of a classical signal sequence (Michiels et al., Infect. Immun. 1990, 58: 2840-9; Michiels and Cornelis, J. Bacteriol. 1991, 173: 1677-85) by T3S System (Michiels et al., J. Bacteriol. 1991, 173: 4994-5009); b) the discovery of a new class of chaperones which assist secretion of some Yop proteins (Wattiau and Cornelis, Mol. Microbiol. 1993, 8: 123-31; Wattiau et al., PNAS 1994, 91: 10493-7; Letzelter et al., EMBO J. 2007, 26: 3015-24); c) the introduction of a reporter system based on the calmodulin-dependant adenylate-cyclase to demonstrate that effectors are injected by the bacterium into the cytosol of target cells (Sory and Cornelis, Mol. Microbiol. 1994, 14: 583-94; Sory et al., PNAS, 1995, 92: 11998-12002; Boland et al., EMBO J. 1996, 15: 5191-5201); d) the demonstration that effector YopP prevents the release of TNF-alpha by macrophages and causes their apoptosis (Mills et al., PNAS 1997, 94: 12638-43; Boland and Cornelis, Infect. Immun. 1998, 66: 1878-84). This was the first demonstration that T3S effectors may have anti-inflammatory properties; e) the demonstration that the length of the injectisome needle is determined by a protein acting as a molecular ruler (Journet et al., Science 2003, 302: 1757-60; Wagner et al., PNAS 2010, 107: 13860-5); f) the demonstration that LcrV, a protective antigen against plague, forms a pentameric structure at the tip of the needle (Mueller et al., Science 2005, 310: 674-6); g) the demonstration of the role of the needle (Mota et al., Science 2005, 307: 1278). h) more recently, the activity of Guy in the field of T3S concerned the assembly and structure of the bacterial injectisome (Sorg et al., EMBO J. 2007, 26: 3015-24; Diepold et al., EMBO J. 2010, 29: 1928-40). In 2004, Guy initiated the study of the pathogenesis of Capnocytophaga canimorsus, a Gram-negative bacterium from the order of Flavobacteria, commonly found in dogs' mouths. This bacterium is responsible for fatal septicemia or meningitis after dog bites or licks. The main observations made so far in the laboratory of Guy are that C. canimorsus resists the assaults of the innate immunity system and elicits little inflammation (Shin et al., J. Infect Dis. 2007, 195: 375-386; Ittig et al., PLoS Pathogens, in press). Strikingly, it appeared that C. canimorsus is endowed with a new mechanism that allows them to feed on glycan chains from host glycoproteins including surface glycoproteins from phagocytes (Mally et al., PLoS Pathog. 2008, 4: e1000164; Manfredi et al., Mol. Microbiol. 2011, 81: 1050-60; Renzi et al., PLoS Pathog. 2011, 7:e1002118). This mechanism not only sustains growth of the pathogen in vivo, but also contributes to neutralize the immune system. These glycan acquisition systems thus represent a new type of bacterial virulence factors.