2014
DOI: 10.1074/jbc.m114.554345
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Lipopolysaccharide Engineering in Neisseria meningitidis

Abstract: Background: LPS biosynthesis modification offers the potential to create detoxified variants with improved immunostimulatory properties. Results: Pentaacyl LPS molecules from pagL ϩ and lpxL1 Ϫ meningococcal mutants were structurally characterized and found to

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Cited by 23 publications
(24 citation statements)
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“…Neisseria meningitidis typically produces hexa-acylated LPS with phosphate and phosphoethanolamine groups appended to the 1 and 4′ position of the lipid A1314. Heterologous expression of LPS modifying enzymes such as PagL or deletion of lipid A biosynthesis enzymes such as LpxL1 and LpxL2 has been used to detoxify the highly active meningococcal LPS1315.…”
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confidence: 99%
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“…Neisseria meningitidis typically produces hexa-acylated LPS with phosphate and phosphoethanolamine groups appended to the 1 and 4′ position of the lipid A1314. Heterologous expression of LPS modifying enzymes such as PagL or deletion of lipid A biosynthesis enzymes such as LpxL1 and LpxL2 has been used to detoxify the highly active meningococcal LPS1315.…”
mentioning
confidence: 99%
“…Heterologous expression of LPS modifying enzymes such as PagL or deletion of lipid A biosynthesis enzymes such as LpxL1 and LpxL2 has been used to detoxify the highly active meningococcal LPS1315. Deletion of LpxL1 was shown to be an advantageous method for detoxifying meningococcal LPS when making meningococcal outer membrane vesicle vaccines, without the need to use a detergent to reduce excess LPS-related reactogenicity16.…”
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“…MM6 cells do not express DC-SIGN (data not shown), and thus the oligosaccharide would not influence binding, internalization, and activity. The basis for the limited effect of lgtB pagL ϩ nOMVs on the IP-10 response compared to the reduced release of proinflammatory cytokines IL-6 and IL-1␤ is unclear, but this has been previously observed for purified pagL LPS (16). Activation of TLR4 and MD-2 very much depends on how the lipid A structure is situated inside the MD-2 pocket and whether the two dimerization interfaces can be formed (31).…”
Section: Discussionmentioning
confidence: 99%
“…1). These penta-acylated lipid A forms show reduced endotoxic activity compared to that of hexa-acylated LPS (16). The combination of rmpM deletion and genetic LPS modification thus enables the isolation of high yields of so-called native OMVs (nOMVs) with reduced endotoxicity without the need for deoxycholate treatment.…”
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confidence: 99%