INTERACTIONS OF MYCOBACTERIAL GLYCOPEPTIDOLIPIDS WITH MEMBRANES - INFLUENCE OF CARBOHYDRATE ON INDUCED ALTERATIONS

Glycopeptidolipids (GPLs) are specific constituents of mycobacteria kn own as opportunistic pathogens. The influence of the carbohydrate moie ty 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 iso lated 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 carb oxyfluorescein (GPL-1 > GPL-2), while GPL-3 and GPL-5 were inactive. G PL-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 is otherms 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 a n increase in the surface pressure, its area decreased, down to that o f a tightly packed acyl chain. It is postulated that the glycopeptidic moiety can be either at in the interface or dipping into the water. G PL-2 insertion in liposomes rendered the acyl-chain part of the bilaye r more accessible to ions, since a fluorescent probe located deep in t he bilayer was much more quenched by Cu2+ ions in liposomes containing GPL-2 than in control liposomes, suggesting a disturbance of the bila yer interface. A model is proposed to explain the influence of the pol arity of GPLs on their activity toward membrane properties.