The physico‐chemical characteristics of the phosphocholine‐containing glycoglycerolipid MfGL‐II govern the permeability properties of Mycoplasma fermentans

Abstract

Mycoplasma fermentans seems to be involved in several pathogenic condtions in humans, and is among other things capable of fusing with T-cells and lymphocytes. The choline-containing phosphoglycolipid 6 H -O-(3 HH -phosphocholine-2 HH -amino-1 HH -phospho-1 HH ,3 HH -propanediol)-a-dglucopyranosyl-(1 H 33)-1,2-diacylglycerol (MfGL-II) in the membrane of M. fermentans has been suggested to enhance the fusion process, and the characteristics of MfGL-II were therefore investigated. When a cell culture ages the fraction of MfGL-II increases, and the fraction of the other major membrane lipid, phosphatidylglycerol (PtdGro), decreases concomitantly. Swelling experiments showed that the permeability and osmotic fragility are markedly reduced in aged cells. MfGL-II is selectively released into the surrounding medium when aged M. fermentans cells are incubated in buffer containing EDTA. The physico-chemical properties of MfGL-II were studied by NMR spectroscopy and differential scanning calorimetry, and they can explain the biochemical results. The temperature for the transition between gel and lamellar liquid crystalline (L a ) phases is 35±45 8C higher for MfGL-II than for PtdGro, which most probably gives rise to the reduced permeability in aged cells. At high water contents MfGL-II forms an L a phase and isotropic aggregates which were interpreted to be vesicles with a radius of < 450 A Ê . It is proposed that MfGL-II forms vesicles in the surrounding medium when it is released from the cell membrane. Neither EDTA nor Ca 21 ions have a significant influence on the aggregate structures formed by MfGL-II. Our results indicate that MfGL-II has no fusogenic properties. It is more probable that a recently identified lysolipid in the M. fermentans membrane acts as a fusogen.Keywords: Mycoplasma fermentans; MfGL-II; cholinecontaining lipids; membrane permeability; physico-chemical properties.The human pathogen Mycoplasma fermentans PG18 was first isolated from the urogenital tract several decades ago [1]. The interest in M. fermentans has recently increased because of reports indicating its possible role as a cofactor accelerating the progression of AIDS, its significance as a pathogen in other immunocompromised patients [2], and its role in the pathogenesis of rheumatoid arthritis [3]. While little is known of the molecular mechanisms underlying M. fermentans pathogenicity [4], it has been shown that HIV-associated cytopathic effects could be increased by the presence of M. fermentans [2], and that M. fermentans is capable of fusing with T-cells and peripheral lymphocytes [5].It is reasonable to assume that mycoplasmal membrane components are involved in the attachment and fusion of the microbe with eukaryotic host cells. Deutch et al. [6] isolated an unusual choline-containing phosphoglycolipid from the cell membranes of M. fermentans strain PG18 and suggested that this lipid was capable of enhancing the fusion of small, unilamellar vesicles with MOLT-3 lymphocytes in a dose-dependent manner. Structural analysis of this l...

Physicochemical characterization and biological activity of a glycoglycerolipid from Mycoplasma fermentans

“…Recently, Ben‐Menachem et al . [45] presented a physico‐chemical characterization of MfGl‐II to study the permeability of M. fermentans . They observed also the existence of a gel‐to‐liquid crystalline phase transition, which they estimated to range between 35 and 45 °C.…”

Interaction of Mycoplasmas With Host Cells

“…It is widely accepted that the reorganization of the membrane structure that occurs during fusion requires that the lipid bilayer is broken up and that other inverted configurations, such as reversed nonbilayer aggregates, are being formed (18,60,97). Nevertheless, analyses of the phase behavior of MfGL-II/H 2 O mixtures by solid state 31 P and pulsed-field gradient diffusion NMR spectroscopy revealed that MfGL-II is a bilayer stabilizing lipid incapable of undergoing a phase transition from a lamellar to an inverted configuration (8). This property of MfGL-II is difficult to reconcile with a role in membrane fusion.…”

An easy α-glycosylation methodology for the synthesis and stereochemistry of mycoplasma α-glycolipid antigens

“…GGPL-I has a structural feature analogous to 1,2-di- O -palmitoyl phosphatidylcholine (DPPC) as a ubiquitous cell membrane phospholipid. Apparently, GGPLs are amphiphilic compounds that can form certain self-assembled structures under physiological conditions [12–13] and may give physicochemical stress on the immune system of the host [17]. In fact, our research team has proven that these α-glycolipid antigens have certain pathogenic functions [18–19].…”