Since many years, my research interests are focused on the biosynthesis pathway of lipid pathogenicity factors of mycobacteria, the mycolic acid-containing compounds, as well as on the modes of action of drugs targetting this pathway. Mycolic acids, extremely long fatty acids, are the major constituants of the outer membrane (mycomembrane) where they play a strategic role in the cell envelope integrity. During my PhD thesis (supervised by Prof. G. Lanéelle, Toulouse University), I have shown that the mycolic acid biosynthesis pathway is the primary target of the firsline drug isoniazid (INH). My post-doc (Prof. W.R. Jacobs, Jr's lab, Albert Einstein College of Medicine, New York) dealt with the identification, and functional and structural characterization of the INH molecular target (InhA protein) as well as one of the resistance mechanisms to INH. I integrated Prof. G. Lanéelle's group at CNRS as a Research Associate in 1995, then became Research Director in Dr. M. Daffé's lab at IPBS. With my colleagues and collaborators, we have contributed to decipher the mode of action of INH on its target. Through the supervision of master and PhD students and post-docs, we have identified and characterized key enzymes of mycolic acid biosynthesis pathway as putative therapeutic targets, and contributed to the knowledge about Fatty Acid Synthase type II and mycolic condensation multienzyme systems as well as the mycolic acid-methyltransferase family. These projects have been supported by grants from the french Agence Nationale de la Recherche (ANR), European consortia, as well as France-USA (NSF) and France-Argentina Cooperation programs; they gave rise to research collaboration with pharmaceutical companies.
This work generated 50 original articles, reviews or book chapters, and 5 patents.