Archaeal Membrane Lipids and Applications


Membrane lipids of Archaea are unique and distinct from those found in Eukarya and Bacteria. The polar lipids consist of isoprenoid chains, 20–40 carbons in length and usually saturated, which are attached via stable ether bonds to the glycerol carbons at the sn‐2,3 positions. Polar head groups differ at the genus level of diversity and consist of mixtures of glyco groups (mainly disaccharides), and/or phospho groups primarily phosphoglycerol, phosphoserine, phosphoethanolamine or phosphoinositol. Phosphocholine headgroups are rarely found. Extremely halophilic archaea are characterised by headgroups consisting of phosphoglycerolphosphate‐O‐methyl, and sulfated‐sugars. Some of these archaea synthesise cardiolipin analogues. The inherent stability and unique features of archaeal lipids makes them a useful biomarker for Archaea within environmental samples, including ocean sediments. The polar lipids of Archaea can be used to make liposomes (closed vesicles referred to as archaeosomes) with characteristics that are useful for applications in biotechnology. Archaeal‐like polar lipids are being synthesised to optimise the properties of archaeosomes to serve as next‐generation adjuvants and drug delivery systems.

Key Concepts:

  • Archaeol (2,3‐diphytanyl‐sn‐glycerol), and variations thereof, define the polar lipids of the domain of life, Archaea.

  • The structures of polar lipids biosynthesised provide a useful taxonomic feature to assign an isolate to the Genus level of classification.

  • New polar lipid structures are being reported as the field expands to encompass novel isolates.

  • These unique polar and neutral isoprenyl lipids can be used as biomarkers of archaea in environmental samples.

  • Archaeal lipids can serve as a rich source for novel molecules not commonly found in nature, such as β‐l‐gulose.

  • Archaeal polar lipid mixtures hydrate to form lipid membrane vesicles (archaeosomes) with bilayer, unilayer or a combination of uni and bilayer structure.

  • Archaeosomes are generally nonfusogenic in vitro, but fusion can be dramatic for certain compositions by exposure to the combination of acidic pH, calcium and glycosidase.

  • Archaeosomes function as safe vaccine adjuvants in mammals imparting long‐lasting CD8+ T‐cell immunity and antibody responses.

  • Isoprenoid lipids that retain the key archaeal‐lipid features are being synthesised to optimise their properties as vaccine adjuvants and delivery systems.

Keywords: archaea; membrane lipids; archaeol; caldarchaeol; biomarkers; archaeosomes; adjuvants; drug delivery

Figure 1.

Structural comparison between a conventional ester lipid and an archaeal diether (archaeol) lipid. PG, phosphoglycerol head group.

Figure 2.

Core lipid structures reported in the domain Archaea. The nomenclature used is for the lipid cores, where X and Y are hydrogen atoms. Polar lipids consist of the above structures, where X and Y are replaced by the various polar head groups.

Figure 3.

Models to depict the organisation of archaeal monopolar and bipolar lipids in a lipid membrane. (a) Monopolar archaeol lipids in a bilayer arrangement, (b) bipolar lipids in a monomolecular layer and (c) mixture of mono‐ and bipolar lipids in a bilayer/monolayer organisation. Reproduced with permission of ASM Press from Figure Sprott and Krishnan .

Figure 4.

Model of an antigen‐presenting cell illustrating how archaeosomes carrying an antigen (Ag) may be taken up following immunisation by receptor (R)‐mediated phagocytosis, and lead to antigen presentation by both MHC class I and II pathways. Following phagosome‐lysosome fusion, a portion of the archaeosomes is broken down to release the antigen for processing within the phagolysosome by acidic proteases and MHC class II presentation of appropriate so‐generated peptides. To explain the observed CD8+ T‐cell response, antigen crosses the phagolysosome membrane for processing in the cytosol via the classical MHC class I presentation pathway (cross‐presentation). Modified Figure reproduced with permission of Oxford University Press (Sprott et al., ).

Figure 5.

Phase‐contrast microscopy images of archaeosomes before (a) and after (b) induction of fusion. Fusion was induced in vitro by three specific parameters: a shift in pH to 4.5 in 140 mm NaCl, 1.0 mm calcium and addition of β‐glucosidase. Magnification is the same for both panels. Archaeosomes in (a) are 66 nm. Reproduced from Figure with permission of Oxford University Press (Sprott et al., ).



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Further Reading

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Whitfield DM, Eichler EE and Sprott GD (2008) Synthesis of archaeal glycolipid adjuvants – what is the optimum number of sugars? Carbohydrate Research 343: 2349–2360.

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Sprott, G Dennis(Aug 2011) Archaeal Membrane Lipids and Applications. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000385.pub3]