My laboratory is focused on infectious diseases, especially human Tuberculosis caused by Mycobacterium tuberculosis (Mtb), which is one of mankind’s most successful intracellular pathogens.
BACKGROUND and RESEARCH
Knowing that the mycobacterial cell envelope is one of the first links in the host-pathogen cross-talk, I did a Ph.D, in Toulouse (France), in order to study the biogenesis of the mycobacterial cell wall, especially the identification of the glycosyltransferases potentially involved in the biosynthesis of (lipo) polysaccharides which constitute the Achilles’ hill of the mycobacterial cell-envelope.
Then, I performed my first post-doctoral project, in Toulouse (France), on the development of non-peptide-based vaccines, using glycolipids-based mycobacterial. During my second post-doctoral project, at MRC-NIMR London (UK), I focused on the “functional annotation” of orphan enzymes in Mtb with the aim of placing previously uncharacterized proteins into specific metabolic pathways by applying an activity-based metabolomic profiling technique. With this methodology we discovered a novel pathway involved in the catabolism of the polar head group of plasma membrane glycerophospholipids. In addition, as part of a collaborative project, we have found that aspartate is required for the virulence of Mtb within the host. Using the same approaches, we have also confirmed that ansP2 encodes an asparagine transporter in Mtb. Asparagine is not only assimilated by Mtb but also hydrolysed by the asparaginase AnsA resulting in the production of ammonia, which aids in the neutralization of phagosomal acidification.
As a lecturer in Molecular Microbiology at the MRC-CMBI, Imperial College, my laboratory explores deciphering the environmental adaptation of Mtb within the host. Mainly Metabolomics, and Transcriptomics, Proteomics, and Lipidomics are used as tools for the read-out of the first steps in this adaptation. Effectively, the success of Mtb as a pathogen partially results from its capacity to invade, survive and persist within intracellular phagosomes and extracellular sites in many host tissues. Throughout the cycle of infection, Mtb encounters and survives in a variety of harsh environments in the human body including nutrient-poor, acidic, oxidative, nitrosative and hypoxic niches. Very little is known about the molecular mechanism and kinetics of adaptation of Mtb during the first stages of infection within the host. Deciphering these mechanisms in such defined environments is crucial to understanding the physiology of Mtb within the host and can also inform on us why Mtb is such an efficient intracellular pathogen. The findings will potentially lead to the discovery of new drug targets and have a better understanding on resistant bacteria in context of the host.
et al., 2016, Cell-Envelope Remodeling as a Determinant of Phenotypic Antibacterial Tolerance in Mycobacterium tuberculosis, Acs Infectious Diseases, Vol:2, ISSN:2373-8227, Pages:352-360
Larrouy-Maumus G, Puzo G, 2015, Mycobacterial envelope lipids fingerprint from direct MALDI-TOF MS analysis of intact bacilli, Tuberculosis, Vol:95, ISSN:1472-9792, Pages:75-85
et al., 2013, Discovery of a glycerol 3-phosphate phosphatase reveals glycerophospholipid polar head recycling in Mycobacterium tuberculosis, Proceedings of the National Academy of Sciences of the United States of America, Vol:110, ISSN:0027-8424, Pages:11320-11325
et al., 2013, Mycobacterium tuberculosis nitrogen assimilation and host colonization require aspartate, Nature Chemical Biology, Vol:9, ISSN:1552-4450, Pages:674-+
et al., 2014, Mycobacterium tuberculosis Exploits Asparagine to Assimilate Nitrogen and Resist Acid Stress during Infection, Plos Pathogens, Vol:10, ISSN:1553-7374
et al., 2014, Biosynthesis and Translocation of Unsulfated Acyltrehaloses in Mycobacterium tuberculosis, Journal of Biological Chemistry, Vol:289, ISSN:1083-351X, Pages:27952-27965
et al., 2012, A Small Multidrug Resistance-like Transporter Involved in the Arabinosylation of Arabinogalactan and Lipoarabinomannan in Mycobacteria, Journal of Biological Chemistry, Vol:287, ISSN:0021-9258
Prosser GA, Larrouy-Maumus G, de Carvalho LPS, 2014, Metabolomic strategies for the identification of new enzyme functions and metabolic pathways, EMBO Reports, Vol:15, ISSN:1469-221X, Pages:657-669