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Review
. 2021 Oct 18;26(20):6294.
doi: 10.3390/molecules26206294.

Lipid A-Mediated Bacterial-Host Chemical Ecology: Synthetic Research of Bacterial Lipid As and Their Development as Adjuvants

Atsushi Shimoyama  1   2 , Koichi Fukase  1   2
Affiliations
Review

Lipid A-Mediated Bacterial-Host Chemical Ecology: Synthetic Research of Bacterial Lipid As and Their Development as Adjuvants

Atsushi Shimoyama et al. Molecules. .

Abstract

Gram-negative bacterial cell surface component lipopolysaccharide (LPS) and its active principle, lipid A, exhibit immunostimulatory effects and have the potential to act as adjuvants. However, canonical LPS acts as an endotoxin by hyperstimulating the immune response. Therefore, LPS and lipid A must be structurally modified to minimize their toxic effects while maintaining their adjuvant effect for application as vaccine adjuvants. In the field of chemical ecology research, various biological phenomena occurring among organisms are considered molecular interactions. Recently, the hypothesis has been proposed that LPS and lipid A mediate bacterial-host chemical ecology to regulate various host biological phenomena, mainly immunity. Parasitic and symbiotic bacteria inhabiting the host are predicted to possess low-toxicity immunomodulators due to the chemical structural changes of their LPS caused by co-evolution with the host. Studies on the chemical synthesis and functional evaluation of their lipid As have been developed to test this hypothesis and to apply them to low-toxicity and safe adjuvants.

Keywords: Alcaligenes faecalis; adjuvant; chemical biology; chemical ecology; glycolipid; lipid A; lipopolysaccharide; natural product chemistry; symbiotic bacteria.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Bacterial–host chemical ecology mediated by lipid A.
Figure 2
Figure 2
E. coli LPS and Kdo-lipid A.
Figure 3
Figure 3
Lipid IVa.
Figure 4
Figure 4
Innate immune activation via TLR4/MD2.
Figure 5
Figure 5
Molecular mechanism of TLR4/MD2 dimerization process.
Figure 6
Figure 6
Chemical structures of various lipid As and lipid A analogs.
Figure 7
Figure 7
Chemical structures of parasitic bacterial lipid As.
Figure 8
Figure 8
Chemical structures of A. faecalis LOS structures.
Figure 9
Figure 9
Chemical structures of synthesized A. faecalis lipid As.
Figure 10
Figure 10
Chemical structures of lipid As in the environment and in fermented foods.
Figure 11
Figure 11
Self-adjuvanting strategy.
Figure 12
Figure 12
Chemical structures of adjuvant-antigen complexes; (A) meningococcal antigen conjugated with MPL adjuvant, (B) Thomsen-Friedenreich antigen conjugated with RC-529 (11) adjuvant, (C) peptide antigen conjugated with CRX-527 adjuvant.
See this image and copyright information in PMC

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