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Logo of jbcThe Journal of Biological Chemistry
 
J Biol Chem. 2010 July 9; 285(28): le11.
PMCID: PMC2898374

Altered Linkage of Hydroxyacyl Chains in Bacterial Lipid A

van Mourik et al. (1) recently deduced that the mixed lipid A of Campylobacter jejuni lipooligosaccharide, containing both glucosamine and diaminoglucose as backbone sugars, induces less cellular activation through the TLR4-MD2 complex than classical enterobacterial lipid A (containing glucosamine alone) and endows this bacterium with greater resistance to antimicrobial peptides, due to the presence of a greater proportion of amide-linked fatty acids in the former lipid A. This is consistent with our previous hypothesis (2) that the presence of three rather than two amide-liked fatty acids in the predominant C. jejuni lipid A species (3) influences a range of observed biological activities (4).

However, van Mourik et al. (1) speculated that a reduced flexibility of the amide-linked acyl chains in C. jejuni lipid A would affect interaction with the TLR4-MD2 complex and thus influence cellular activation. Our previous studies have shown that the phase transition at 37° C of C. jejuni compared to enterobacterial lipopolysaccharide is lower, reflecting the presence of longer non-hydroxylated acyl chains (4), but the three-dimensional supramolecular conformation of lipid A, which is not only influenced by amide linkage of acyl chains, but also by the phosphate and polar head group substitution of the lipid A backbone, as well as by acyl chain distribution and lengths, can be correlated with the lower biological activities of C. jejuni lipid A (5). Moreover, as demonstrated recently (6), C. jejuni susceptibility to antimicrobial peptides can be influenced by phosphoethanolamine substitution in lipid A. Thus, the role of other structural features of diaminoglucose-containing lipid A, combined with hydroxyacyl linkage, require further investigation to fully understand their contributory role to lipid A structure-bioactivity relationships.

References

1. van Mourik A., Steeghs L., van Laar J., Meiring H. D., Hamstra H.-J., van Putten J. P. M., Wösten M. M. S. M. (2010) J. Biol. Chem. 285, 15828–15836 [PMC free article] [PubMed]
2. Moran A. P. (1997) J. Infect. Dis. 176, Suppl. 2, S115–S121 [PubMed]
3. Moran A. P., Zähringer U., Seydel U., Scholz D., Stütz P., Rietschel E. T. (1991) Eur. J. Biochem. 198, 459–469 [PubMed]
4. Moran A. P. (1997) FEMS Immunol. Med. Microbiol. 11, 121–130 [PubMed]
5. Schromm A. B., Brandenburg K., Loppnow H., Moran A. P., Koch M. H. J., Rietschel E. T., Seydel U. (2000) Eur. J. Biochem. 267, 2008–2013 [PubMed]
6. Cullen T. W., Trent M. S. (2010) Proc. Natl. Acad. Sci. U. S. A. 107, 5160–5165 [PubMed]

Articles from The Journal of Biological Chemistry are provided here courtesy of American Society for Biochemistry and Molecular Biology