Fig. 1.

The cell wall of Mycobacterium tuberculosis. The inner leaflet of the plasma membrane contains a high quantity of Ac₁/Ac₂PIM₂ (tri- and tetra-acylated phosphatidyl-myo-inositol-dimannoside), while the outer membrane has Ac₁/Ac₂PIM₆ (tri- and tetra-acylated phosphatidyl-myo-inositol-hexamannoside), along with the more usual phospholipids, DPG (diphosphatidylglycerol), PE (phosphatidylethanolamine) and PI (phosphatidylinositol); the methyl groups of the unique tuberculostearic acids of mycobacteria are depicted here (Minnikin et al., 2015). Also anchored into the plasma membrane are LM (lipomannan) and LAM (lipoarabinomannan), which project out into the periplasm; the mannose sugars and mannan domains are coloured light blue and the branched arabinan is green. According to the ‘scaffold model’, the glycan back bone (purple) of the PG (peptidoglycan) forms a matrix of helices orientated perpendicular to the plasma membrane (Dmitriev et al., 2000). These surround the AG (arabinogalactan) and LAM (lipoarabinomannan) and are connected by the peptide cross-links (coloured circles: orange = L-alanine, yellow = D-isoglutamine, green = meso-diaminopimelate and blue = D-alanine). The PG is connected to the base of the Gal (galactan; orange) via a unique rhamnose-N-acetylglucosamine linker. Three highly branched Ara (arabinan; green) domains project from the base of the Gal towards the MA layer (mycolic acids; dark blues and purples), which is covalently attached to most of the non-reducing ends of the Ara and forms the inner layer of the MOM (mycobacterial outer membrane). The PG, AG and MA make up the mycolylarabinogalactan-peptidoglycan complex (mAGP). The free lipids of the outer leaflet consist of PDIM (phthiocerol dimycocerosates); DAT, TAT, PAT and SGL (di-, tri- and penta-acyl trehalose and sulfated trehalose glycolipids) (Jankute et al., 2015, Minnikin et al., 2015). The diagram is roughly to scale using dimensions obtained from cryo-electron microscopy (Zuber et al., 2008). The main current and pipe-line drugs targeting the biosynthesis/transport pathways of the cell wall are shown in red. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)