Biography of Guy R. Cornelis

Guy R. Cornelis graduated as a pharmacist from the University of Louvain (Belgium). As a scholar of the Belgian National Science Foundation, he studied β-lactamases with Sir E.P. Abraham at the W. Dunn School of Pathology (Oxford UK) and received his doctoral degree from the University of Louvain (1974). He then studied antibiotic resistance plasmids with Sir M.K. Richmond at the University of Bristol (UK), and bacterial transposons with H. Saedler at the University of Freiburg (D) and later at the Max Planck Institute in Cologne (D). The highlight of this period was the discovery of a transposon encoding lactose fermentation (editorial in Nature, 1978 274: 211). In 1984, Guy R. Cornelis was appointed as Lecturer at the University 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 Umeå, Sweden, and presented by the two authors in a common review article in 1997 (Cornelis and Wolf-Watz, Mol. Microbiol., 1997, 23: 861-67).

T3S is a mechanism by which many Gram-negative bacteria inject "effector" proteins into the cytosol of animal, plant or insect cells. The effectors disarm or reprogram the target cell by sabotaging or hijacking 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. Y. enterocolitica and Y. pestis 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 R. Cornelis' laboratory are (i) 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 a new type of secretion system, now known as the "type III secretion system" (T3SS) (Michiels et al., J. Bacteriol. 1991, 173: 4994-5009); (ii) 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); (iii) 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 eukaryotic 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); (iv) the demonstration that one of the effectors (YopP) prevents the release of TNF-α by macrophages and causes apoptosis of macrophages (Mills et al., PNAS 1997, 94: 12638-43; Boland and Cornelis, Infect. Immun. 1998, 66: 1878-84). This was the very first demonstration that T3S effectors may have anti-inflammatory properties; (v) 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: 1757-1760; Wagner et al., PNAS 2010, 107: 13860-5); (vi) 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: 674-676); (viii) the demonstration of the role of the needle (Mota et al., Science 2005, 307: 1278). More recently, the activity of Guy R. Cornelis 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). Reviews on T3S and the injectisome were invited by Nature Reviews Molecular and Cell Biology 2002 46: 1183-1197, by the Journal of Cell Biology 2002, 45: 805-815 and by Nature Reviews Microbiology 2006, 4: 811-825;

In 2004, Guy R. Cornelis 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. An overview of case reports suggests that the bacterium induces little inflammation during the early stages of the infection, until overwhelming bacterial growth and spread finally causes shock or meningitis. The main observations made so far in the laboratory of Guy R. Cornelis are that C. canimorsus resists the assaults of the innate immunity system and elicits little inflammation, which probably allows the silent onset of the infection (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.

Guy R. Cornelis was appointed Professor (1992) and Ordinary Professor (1997) of the University of Louvain where he chaired the Department of Microbiology-Immunology (1993-2000) and the Graduate School of Biochemistry, Cell Biology and Microbiology (1999-2000). Between 1991 and 2002, his research on Yersinia pathogenesis was conducted at the "Christian de Duve Institute of Cell Pathology" in Brussels. In 2000 he was appointed Ordinary Professor of the University of Basel in Switzerland and in 2001 moved his laboratory to the Biozentrum, where he chaired the Focal Area Infection Biology from 2004 until 2011.

Guy R. Cornelis has authored 140 peer-reviewed original papers, 27 peer-reviewed reviews, 39 chapters of books or monographs and collected 12'554 citations (h-index = 62). During this work, he has mentored 31 PhD students and 25 Post-docs. His alumni hold academic positions in Brussels (B), Corvallis (OR, USA), Edmonton (Canada), Galway (Ir), Hannover (D), Lisbon (P), Namur (B), Nottingham (UK), Pamplona (Sp), Paris (F), Toulouse (F) and Utrecht (Nl).

 He has served on many scientific advisory boards, including that of the "Institut Pasteur" (1987-1991). He has been an EMBO member since 1998. He served as the "European Chair" of the GORDON Research Conference on Molecular Mechanisms of Bacterial Signalling and Adhesion (1999). Since 2005, he has been listed among the highly-cited scientists by the ISI Web of Knowledge. In 2008, Guy R. Cornelis was elected as a fellow of the American Academy for Microbiology. In 2011, he was awarded an "Advanced Grant" from the European Research Council (ERC) to pursue his study of the molecular aspects of the human infections by C. canimorsus. After his retirement from the University of Basel in 2012, his research will be continued at the "Facultés Universitaires Notre-Dame de la Paix”, in Namur, Belgium.