Understanding the role of the mycobacterial envelope in pathogenicity and targeting this particularly low permeable structure represents a key step towards anti-TB therapy. This requires, however, the structural determination of its individual components as well as their mapping, organization, and roles.
Our expertise in structural determination allows us to take the lead in detecting, quantifying, characterizing and disclosing biological activities of many lipids and glycoconjugates of the mycobacterial envelope. Among them: essential mycolic acids (α-alkyl, β-hydroxylated very-long chain (up to C100) fatty acids containing various decorations), phenolycolipids (PGL), phthiocerol dimycocerosate (DIM), capsular alpha-glucan, lipopeptides, phtiocol, trehalose-polyphleates (PPT), -monomycolate (MMT) or –dimycolate (DMT), lipooligosaccharides (LOS), and others.
The biosynthesis and the biological activities (permeability, virulence,…) of these constituents are investigated going through obtaining and analyzing mutants.
How do these components organize?
Our demonstration of the occurrence of a capsule layer above the mycobacterial cell wall, and of an outer membrane (called mycomembrane, MM) now enlightens some of the unique properties of mycobacteria, such as their very low permeability to nutrients and hydrophilic drugs. Although many constituents of the mycobacterial envelope have been described, the question of their specific location, where and how, remains to be elucidated. To address this question, we developed methods to isolate the capsule and MM-containing cell wall fractions and their constituents. Their analysis helps understanding how the different molecules can organize within the envelope.
- R. Brosch's group, Institut Pasteur, Paris
- V. Gervais and A. Milon’s group, Institut de Pharmacologie et Biologie Structurale
- O. Schiltz's group, Institut de Pharmacologie et Biologie Structurale, Toulouse
- S.H.E Kaufmann’s group, Max Planck Institute for Infection
- B. Zuber’s group, University of Bern
- C. Guilhot's group, Institut de Pharmacologie et Biologie Structurale, Toulouse
- F. Biet’s group INRA, Université de Tours
- Chiaradia L, et al., (2017) Dissecting the mycobacterial cell envelope and defining the composition of the native mycomembrane. Sci Rep, 7:12807
- Carel, C. et al (2017) Identification of specific posttranslational O-mycoloylations mediating protein targeting to the mycomembrane. Proc Natl Acad Sci U S A. 18,, 4231-4236
- Lefebvre C et al (2018) HadD, a novel fatty acid synthase type II protein, is essential for alpha- and epoxy-mycolic acid biosynthesis and mycobacterial fitness. Sci Rep 8:6034
- Slama N et al (2016) The changes in mycolic acid structures caused by hadC mutation have a dramatic effect on virulence of Mycobacterium tuberculosis. Mol Microbiol 99:794-807
- Moura-Alves P et al., (2014). AhR sensing of bacterial pigments regulates antibacterial defence. Nature 512:387-92
- Bannantine, et al., (2017) Cell wall peptidolipids of Mycobacterium avium: from genetic prediction to exact structure of a nonribosomal peptide. Mol Microbiology 105, 525-539
- Burbaud, S. et al., (2016) Trehalose Polyphleates Are Produced by a Glycolipid Biosynthetic Pathway Conserved across Phylogenetically Distant Mycobacteria. Cell chemical biology 23, 278-289
- Laneelle et al. (2013) Structural elucidation and genomic scrutiny of the C60-C100 mycolic acids of Segniliparus rotundus. Microbiology 159 (Pt 1):191-203.
Selected reviews/book chapters
- Daffé M & Marrakchi H (2018) Unraveling the structure of the Mycobacterial Envelope. In Gram Positive Pathogens 3rd edition (ASM Press)
- Daffé, M. (2015) The cell envelope of tubercle bacilli, Tuberculosis, 95, 155-8
- Daffé, M, Crick, DC, Jackson, M. (2014) Genetics of capsular polysaccharides and cell envelope (glycol) lipids Microbiol Spectr., 2, 1-46.