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Microbiologists everywhere are saddened by the recent loss of Jean-Marc Reyrat, one of their most valued colleagues, who died after a short but brave battle against cancer. Qualities that come to mind when one remembers Jean-Marc are enthusiasm, strong motivation for scientific research, original thinking, critical assessment of his own work, integrity, fairness, loyalty and dedication to young scientists.
Jean-Marc fell in love with bugs in the early 1990s while studying Microbiology in Toulouse University, where he made his first steps in research in Pierre Boistard's lab. There, Jean-Marc dissected out regulatory mechanisms of nitrogen fixation by the symbiotic bacterium Rhizobium meliloti (Reyrat et al., 1993; 1994;). His love for bacteria broadened thereafter to include many different types.
After completing his PhD in 1993, Jean-Marc went for a long trip in the Middle-East (back-packing was one of his passions) before joined Brigitte Gicquel's group at the Institut Pasteur in Paris to work on one of the major infectious agents affecting mankind, Mycobacterium tuberculosis. At that time, this slow growing, GC-rich bacterium was genetically almost totally intractable, and the scientific community doubted whether it would ever be possible to create null mutants. Here, one of Jean-Marc's characteristic traits came into play: never listen to what people say, just try yourself. Taking the urease gene of Mycobacterium bovis Bacille Camette-Guérin as a model, Jean-Marc was the first to demonstrate the feasibility of knocking out a gene in slow-growing mycobacteria (Reyrat et al., 1995). Together with Vladimir Pelicic, then a PhD student in the same laboratory, Jean-Marc decided to test the possibility of using the Bacillus subtilis sacB gene encoding levansucrase as a counter-selectable marker. They reasoned that although mycobacteria are generally referred to as Gram-positive bacteria, their complex cell wall creates an outer membrane and, hence a periplasmic-like space that could render them sensitive to accumulation of levan produced from sucrose by levansucrase in the inter-membrane compartment. This prediction was validated, and the strategy was used to create null mutants of members of the M. tuberculosis complex. This powerful genetic tool was soon put to use by many mycobacterial geneticists to improve the selection of gene-replacement events in slow-growing mycobacteria. These major breakthroughs were reported in seminal papers (Pelicic et al., 1996a,b;) and opened the way for the construction of allelic exchange mutants to identify M. tuberculosis virulence determinants.
Jean-Marc then decided to shift to another pathogenic bacterium, Helicobacter pylori, the major cause of stomach ulcers and strongly associated with gastric cancer. In 1996, he obtained a Marie Curie fellowship to join the renowned vaccine research centre of the Chiron Corporation – today Novartis – directed by Rino Rappuoli in Siena. He joined the team supervised by John Telford and studied the vacuolating cytotoxin, a major virulence factor encoded by the vacA gene in pathogenic H. pylori. In the 5 years that he spent in Siena, he made major contributions to the understanding of the function, cell specificity and the complex 3D structure of the VacA cytotoxin (Pagliaccia et al., 1998; Reyrat et al., 1999). Jean-Marc enjoyed the ‘dolce vita’ under the wonderful Tuscan sky.
After obtaining a permanent position in INSERM, the French National Institute of Health and Medical Research, Jean-Marc returned to the Institut Pasteur in 1998 to work again on mycobacteria. In 2003, he joined Xavier Nassif's INSERM unit at the Necker Faculty of Medicine, little over a stone's throw from the Institut Pasteur in Paris, as a young independent scientist in the highly competitive INSERM Avenir award scheme to develop his research project on Mycobacterium smegmatis, a non-pathogenic species that shares some genetic traits with pathogenic M. tuberculosis. The gamble was to use M. smegmatis as a model to dissect the molecular pathways for the synthesis of complex lipids that form a major component of the mycobacterial envelope (Reyrat and Kahn, 2001). Jean-Marc was very successful in this GAME (Genetic Analysis of the Mycobacterial Envelope) and published a series of important papers describing the pathways involved in the biosynthesis of some key molecules involved in communication with the host cell, such as glycopeptidolipids (Deshayes et al., 2005; Sondèn et al., 2005; Provvedi et al., 2008). Recently, he turned to Mycobacterium abscessus, an emerging pathogen in cystic fibrosis patients that produces similar small key lipid molecules (Medjahed and Reyrat, 2009).
Jean-Marc was promoted Directeur de Recherche by INSERM in 2008 and was to be appointed to head his own INSERM team starting in 2010. Jean-Marc was a brilliant scientist, keen to understand the genetic basis of virulence in important human pathogens, as illustrated by his list of publications and the recent edition, with Mamadou Daffé, of a book on the Mycobacterial Cell Envelope (Daffé and Reyrat, 2008). However, restricting recognition of his dedication to science to the publication of papers in high-ranked journals would be unfair. Jean-Marc always found time to share with young people his enthusiasm for microbes and genetics. He created a course for young scientists to teach the use of bioinformatic tools. Probably the most prestigious achievement along this line was the ‘Young Scientist Symposia’ that Jean-Marc and his colleagues created in 2005. This 1 day congress was so well appreciated that five sessions were organized since 2005. The meeting this year, on September 29, was the last time Jean-Marc attended this gathering of young scientists that he initiated. One month later, Jean-Marc, aged 42 years, left us. We miss him deeply.