Interactions of Mycobacterial Glycopeptidolipids with Membranes: Influence of Carbohydrate on Induced Alterations

Glycopeptidolipids (GPLs) are specific constituents of mycobacteria known as opportunistic pathogens. The influence of the carbohydrate moiety on GPL-induced membrane alterations was examined with GPLs bearing 1-5 sugar residues (GPL-1 to GPL-5) and a sulfated GPL (S-GPL-2). GPLs decreased the ADP/O ratio and increased controlled respiration of isolated mitochondria. The more polar GPLs were the less active, with the following order of efficiency: GPL-1 > GPL-2 > S-GPL-2 = GPL-3 = GPL-5. GPL-1 and GPL-2 increased passive permeability of liposomes to carboxyfluorescein (GPL-1 > GPL-2), while GPL-3 and GPL-5 were inactive. GPL-2 and GPL-3 decreased the transmembrane electrical potential (delta psi) in isolated mitochondria (GPL-2 > GPL-3). These results suggest that GPLs uncouple oxidative phosphorylation by increasing the passive permeability of the mitochondrial membrane to protons. Compression isotherms of GPL-2 monolayers showed that, at low surface pressure, the area per GPL-2 molecule was about 5 times that of an acyl chain: it is likely that the peptide moiety was at the air/water interface. With an increase in the surface pressure, its area decreased, down to that of a tightly packed acyl chain. It is postulated that the glycopeptidic moiety can be either at in the interface or dipping into the water.