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Mar. Drugs 2013, 11(9), 3197-3208; doi:10.3390/md11093197

Influence of Lipid A Acylation Pattern on Membrane Permeability and Innate Immune Stimulation

1 State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China 2 Department of Microbial Pathogenesis, University of Maryland Dental School, Baltimore, MD 21201, USA
* Author to whom correspondence should be addressed.
Received: 30 June 2013 / Revised: 29 July 2013 / Accepted: 9 August 2013 / Published: 26 August 2013
(This article belongs to the Special Issue Marine Lipopolysaccharides)
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Lipid A, the hydrophobic anchor of lipopolysaccharide (LPS), is an essential component in the outer membrane of Gram-negative bacteria. It can stimulate the innate immune system via Toll-like receptor 4/myeloid differentiation factor 2 (TLR4/MD2), leading to the release of inflammatory cytokines. In this study, six Escherichia coli strains which can produce lipid A with different acylation patterns were constructed; the influence of lipid A acylation pattern on the membrane permeability and innate immune stimulation has been systematically investigated. The lipid A species were isolated and identified by matrix assisted laser ionization desorption-time of flight/tandem mass spectrometry. N-Phenyl naphthylamine uptake assay and antibiotic susceptibility test showed that membrane permeability of these strains were different. The lower the number of acyl chains in lipid A, the stronger the membrane permeability. LPS purified from these strains were used to stimulate human or mouse macrophage cells, and different levels of cytokines were induced. Compared with wild type hexa-acylated LPS, penta-acylated, tetra-acylated and tri-acylated LPS induced lower levels of cytokines. These results suggest that the lipid A acylation pattern influences both the bacterial membrane permeability and innate immune stimulation. The results would be useful for redesigning the bacterial membrane structure and for developing lipid A vaccine adjuvant.
Keywords: endotoxin; lipid A; lipopolysaccharide; TLR4/MD2; membrane permeability; PagL endotoxin; lipid A; lipopolysaccharide; TLR4/MD2; membrane permeability; PagL
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Li, Y.; Wang, Z.; Chen, J.; Ernst, R.K.; Wang, X. Influence of Lipid A Acylation Pattern on Membrane Permeability and Innate Immune Stimulation. Mar. Drugs 2013, 11, 3197-3208.

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