Mycobacteria glycolipids as potential pathogenicity effectors: alteration of model and natural membranes

Abstract

Four mycobacterial wall glycolipids were tested for their effects on phospholipidic liposome organization and passive permeability and on oxidative phosphorylation of isolated mitochondria. From fluorescence polarization of diphenylhexatriene performed on liposomes it was concluded that the two trehalose derivatives (dimycoloyltrehalose and polyphthienoyltrehalose) rigidified the fluid state of liposomes, the triglycosyl phenolphthiocerol slightly fluidized the gel state, while the peptidoglycolipid ("apolar" mycoside C) just shifted the phase transition temperature upward. Dimycoloyltrehalose was without effect on liposome passive permeability, as estimated from dicarboxyfluorescein leak rates, and polyphthienoyltrehalose and triglycosyl phenolphthiocerol slightly decreased leaks, while mycoside C dramatically increased leaks. Activity of these lipids on mitochondrial oxidative phosphorylation was examined. The two trehalose derivatives have been tested previously: both had the same type of inhibitory activity, dimycoloyltrehalose being the most active. Triglycosyl phenolphthiocerol was inactive. Mycoside C was very active, with effects resembling those of classical uncouplers: this suggested that its activity on mitochondria was related to its effect on permeability. All these membrane alterations were called nonspecific because it is likely that they result from nonspecific lipid-lipid interactions, and not from recognition between specific molecular structures. Such nonspecific interactions could be at the origin of some of the effects of mycobacteria glycolipids on cells of the immune system observed in the last few years.

A Mycobacterial Gene Involved in Synthesis of an Outer Cell Envelope Lipid Is a Key Factor in Prevention of Phagosome Maturation

“…Our results revealed that an as-yet-uncharacterized gene adjacent to putative hydrolase and carboxylase genes is involved in lipid metabolism. We concluded that the lipid moiety missing in the P1 mutant participates in impeding PM, as previous reports have shown that mycobacterial lipids can modify membranes (35) and also prevent actin nucleation, which is necessary for PM (1).…”

Surface-exposed Glycopeptidolipids of Mycobacterium smegmatis Specifically Inhibit the Phagocytosis of Mycobacteria by Human Macrophages

“…GPLs from M. avium, essentially through its lipopeptide fragment, have been reported to disturb cell membrane ultrastructure and to change the expression of surface receptors of murine macrophages (43). In addition, mycobacterial GPLs are able to get inserted into phospholipid monolayers (44) and to disturb its properties (45). Such an insertion of molecules may alter interactions of mycobacteria with their host cell.…”

Identification of the surface-exposed lipids on the cell envelopes of Mycobacterium tuberculosis and other mycobacterial species

“…PGLs have been shown to inhibit the lymphoproliferative response (26,44), to suppress monocyte oxidative responses (56), and to scavenge oxygen radicals (47). Similarly, GPLs, which are mainly the most simple version of these molecules, have been shown to inhibit both the nonspecific mitogen-induced proliferation of mononuclear cells (10) and mitochondrial oxidative phosphorylation (55). Keeping in mind that bacterial pathogenicity and virulence are multifactorial, it is not surprising that some nonpathogenic mycobacterial species, like M. gastri, synthesize PGLs (15, 57), whereas both virulent smooth transparent and avirulent smooth opaque strains of M. avium-M. intracellulare elaborate GPLs (5), as does the nonpathogenic M. smegmatis (17), while some virulent strains are devoid of these glycolipids (15,18,53).…”