ArticleScientific reports2016
Modulating endotoxin activity by combinatorial bioengineering of meningococcal lipopolysaccharide.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed.
- Review
- A Sensitive GC-MS Method for Quantitation of Lipid A Backbone Components and Terminal Phosphate Modifications.Journal of the American Society for Mass Spectrometry · 2022Article
- Validation of an FFF-MALS Method to Characterize the Production and Functionalization of Outer-Membrane Vesicles for Conjugate Vaccines.Analytical chemistry · 2022Article
- Regulated Expression ofInternational journal of molecular sciences · 2022Article
- DissectingFrontiers in cellular and infection microbiology · 2022Article
- Lipid A heterogeneity and its role in the host interactions with pathogenic and commensal bacteria.microLife · 2022Review
- Surface Glucan Structures inMarine drugs · 2021Review
- Presence of 2-hydroxymyristate on endotoxins is associated with death in neonates withiScience · 2021Article
- Rational Vaccine Design in Times of Emerging Diseases: The Critical Choices of Immunological Correlates of Protection, Vaccine Antigen and Immunomodulation.Pharmaceutics · 2021Review
- Membrane Microvesicles as Potential Vaccine Candidates.International journal of molecular sciences · 2021Review
- Exploring electrostatic patterns of human, murine, equine and canine TLR4/MD-2 receptors.Innate immunity · 2020Article
- Application of Outer Membrane Protein-Based Vaccines Against Major Bacterial Fish Pathogens in India.Frontiers in immunology · 2020Review
- Substrate structure-activity relationship reveals a limited lipopolysaccharide chemotype range for intestinal alkaline phosphatase.The Journal of biological chemistry · 2019Article
- Pushing the envelope: LPS modifications and their consequences.Nature reviews. Microbiology · 2019Review
- Sulfate depletion triggers overproduction of phospholipids and the release of outer membrane vesicles by Neisseria meningitidis.Scientific reports · 2019Article
- Synthetic glycan-based TLR4 agonists targeting caspase-4/11 for the development of adjuvants and immunotherapeutics.Chemical science · 2018Article
- Diverse pro-inflammatory endotoxin recognition systems of mammalian innate immunity.F1000Research · 2018Review
- Biosynthesis and structure-activity relationships of the lipid a family of glycolipids.Current opinion in chemical biology · 2017Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neisseria meningitidis contains a very potent hexa-acylated LPS that is too toxic for therapeutic applications. We used systematic molecular bioengineering of meningococcal LPS through deletion of biosynthetic enzymes in combination with induction of LPS modifying enzymes to yield a variety of novel LPS mutants with changes in both lipid A acylation and phosphorylation. Mass spectrometry was used for detailed compositional determination of the LPS molecular species, and stimulation of immune cells was done to correlate this with endotoxic activity. Removal of phosphethanolamine in lipid A by deletion of lptA slightly reduces activity of hexa-acylated LPS, but this reduction is even more evident in penta-acylated LPS. Surprisingly, expression of PagL deacylase in a penta-acylated lpxL1 mutant increased LPS activity, contradicting the general rule that tetra-acylated LPS is less active than penta-acylated LPS. Further modification included expression of lpxP, an enzyme known to add a secondary 9-hexadecenoic acid to the 2' acyl chain. The LpxP enzyme is temperature-sensitive, enabling control over the ratio of expressed modified hexa- and penta-acylated LPS by simply changing the growth temperature. These LPS derivatives display a broad range of TLR4 activity and differential cytokine induction, which can be exploited for use as vaccine adjuvant or other TLR4-based therapeutics.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.