Frédéric BRINGAUD

Information

Scientific interests and projects

Our group has been working for over 25 years on molecular biology and metabolism of trypanosomes, with a particular interest on the central and energy metabolism of the procyclic (PCF) and bloodstream (BSF) forms of Trypanosoma brucei. One of our main objectives is to elucidate the topology of the metabolic network, including the discovery of new metabolic pathways and the understanding regulations between different metabolic branches. The group is one of the few in the field of parasitology to have developed a combination of state-of-the-art nuclear magnetic resonance (NMR) and mass spectrometry (MS) metabolomic technologies to study metabolism of wild-type parasites, as well as a large collection mutants (single, double and triple mutants) covering most of the known branches of the central metabolism.

Among our recent major acheivements, we have shown that (1) BSF can grow in medium containing glycerol instead of glucose, while glucose was considered the only carbon source used by the parasite in vivo (Pineda et al., 2018). This open new avenues for understanding parasite metabolism in vivo, as it has recently been described that BSF are more abundant in skin and adipose tissues than in blood. Since the adipocytes present in these organs are excellent glycerol-producers, we study the role of glycerol metabolism in the context of extravascular trypanosomes. (2) Gluconeogenesis occurs in PCF and BSF trypanosomes grown in glucose-free conditions, through unexpected redundant pathways under study (Wargnies et al., 2018). (3) As opposed to most organisms, PCF prefer to metabolise glycerol than glucose, and glycerol metabolism represses glucose consumption through a new mechanism name "metabolic contest" (submitted for publication). Interestingly, phospholipases excreted by PCF can produce glycerol from serum-derived phospholipids that could offer a metabolism benefit in vivo, which is under investigation

Top 5 publications of the last 5 years

1. Wargnies M., E. Bertiaux, E. Cahoreau, N. Ziebart, A. Crouzols, P. Morand, M. Biran, S. Allmann, J. Hubert, O. Villafraz, Y. Millerioux, N. Plazolles, C. Asencio, L. Riviere, B. Rotureau, M. Boshart, J.-C. Portais & F. Bringaud (2018) Gluconeogenesis is essential for trypanosome development in the tsetse fly vector. PLoS Pathog. 14:e1007502. 10.1371/journal.ppat.1007502

2. Pineda E., M. Thonnus, M. Mazet, A. Mourier, E. Cahoreau, M. Biran, J.-W. Dupuy, C. Massante, S. Allmann, L. Riviere, B. Rotureau, J.-C. Portais & F. Bringaud (2018) Glycerol supports growth of the Trypanosoma brucei bloodstream forms in the absence of glucose: analysis of metabolic adaptations on glycerol-rich conditions. PLoS Pathog. 14:e1007412. 10.1371/journal.ppat.1007412

3. Millerioux Y., M. Mazet, G. Bouyssou, S. Allmann, T.R. Kiema, C. Thapa, M. Biran, N. Plazolles, L. Fouillen, E. Bertiaux, A. Crouzols, R. Wierenga, B. Rotureau, P. Moreau & F. Bringaud (2018) De novo biosynthesis of lipids in the Trypanosoma brucei procyclic form: carbon source preferences and metabolic flux redistributions and essentiality of the leucine degradation pathway in vivo. PLoS Pathog. 14:e1007116. 10.1371/journal.ppat.1007116

4. Suárez Mantilla B., L. Marchese, N.A. Dyer, N. Ejeh, M. Biran, F. Bringaud, M.J. Lehane, A. Acosta-Serrano & A. Silber (2017) Trypanosoma brucei proline metabolism is essential for colonization of the tsetse. PLoS Pathog. 13:e1006158. 10.1371/journal.ppat.1006158

5. Creek D.J., M. Mazet, F. Achcar, J. Anderson, D.-H. Kim, R. Kamour, P. Morand, Y. Millerioux, M. Biran, E. Kerkhoven, U. Chokkathukalam, K.E.V. Burgess, R. Breitling, D.G. Watson, F. Bringaud & M.P. Barrett (2015) Untargeted stable isotope labelled metabolomics reveals glucose to contribute widely to the metabolic network of bloodstream form Trypanosoma brucei. PLoS Pathog. 11:e1004689. 10.1371/journal.ppat.1004689