Trans-cyclopropanation of mycolic acids on trehalose dimycolate suppresses Mycobacterium tuberculosis-induced inflammation and virulence

Granulocyte–macrophage colony stimulating factor-mediated innate responses in tuberculosis

“…While intense submucosal infiltration was observed in H37Rv-infected GMKO mice 14 days after infection ( Figure 4H), indicating an effort to establish local cell-mediated immunity, these infiltrates remained unencumbered by the ongoing epithelial destruction in the parenchyma. Virulent mycobacteria have well-known abilities to suppress macrophages, [52][53][54] which may have contributed to local paralysis of macrophage responses and paracrine protection of alveolar epithelial cells in GMKO mice. On the other hand, previous studies showed that alveolar Type II epithelial cells and macrophages collaborate in the translocation of mycobacteria into distal lung parenchyma.…”

Towards understanding the functional diversity of cell wall mycolic acids of Mycobacterium tuberculosis

“…This establishes cmaA2 dependent trans-cyclopropanation of MA as an activity to suppress M. tuberculosis induced inflammation and virulence. Moreover, the stereochemistry of the cyclopropane changes the interaction with the host cell to influence host innate immune responses both positively and negatively [76,77].…”

Lepromatous leprosy patients produce antibodies that recognise non-bilayer lipid arrangements containing mycolic acids

“…Taking into account the molecular form of phospholipids and their molecular arrangements, we proposed that MAs can also have a conical molecular shape (Fig. 1C, D) because they are fatty acids with long hydrocarbon chains (60-90 carbon residues) and also branched beta-hydroxy acids with cyclopropane, methoxy or ketone groups (Minnikin & Goodfellow 1980, Besra & Chatterjee 1994, Barry et al 1998, Rao et al 2006). We further hypothesised that they could induce the formation of non-bilayer lipid arrangements on liposomes (Fig.…”

“…The cellular membrane of M. leprae contains two characteristic lipopolysaccharides (lipoarabinomannan and lipomannan), whereas the cell wall consists of peptidoglycan covalently bound to arabinogalactan, and mycolic acids (MAs). The capsule contains a high level of mycobacterium-specific lipids, which are related to virulence and antibiotic resistance, including phthiocerol dimycocerosate, trehalose mycolates (including chord factor), trehalose sulpholipids (SL), phenolic glycolipid-1 (PGL-1) and MAs (Brennan & Barrow 1980, Britton et al 2000, Ng et al 2000, Rao et al 2006, Scollard et al 2006.…”

“…There are three main types of MAs: alpha, methoxy and keto. Alpha-MAs comprise at least 70% of the MAs present in mycobacteria and contain several cyclopropane rings; methoxy-MAs with several methoxy groups comprise between 10-15% of the MAs and the remaining 10-15% are keto-MAs, which contain several ketone groups (Minnikin & Goodfellow 1980, Besra & Chatterjee 1994, Barry et al 1998, Rao et al 2006, Brennan & Crick 2007. Considering the abundance of mycobacteria in the organs of LL patients (3 x 10 10 /g of tissue) (Waters et al 1978), it is not surprising that some antibodies are directed against lipid-rich mycobacterial antigens.…”