Altered linkage of hydroxyacyl chains in lipid A of Campylobacter jejuni reduces TLR4 activation and antimicrobial resistance.

Modification of the lipid A moiety of bacterial lipopolysaccharide influences cell wall properties, endotoxic activity, and bacterial resistance to antimicrobial peptides. Known modifications are variation in the number or length of acyl chains and/or attached phosphoryl groups. Here we identified two genes (gnnA and gnnB) in the major foodborne pathogen Campylobacter jejuni that enable the synthesis of a GlcN3N precursor UDP 2-acetamido-3-amino-2,3-dideoxy-alpha-D-glucopyranose (UDP-GlcNAc3N) in the lipid A backbone.

Variation of Neisseria gonorrhoeae lipooligosaccharide directs dendritic cell-induced T helper responses.

Gonorrhea is one of the most prevalent sexually transmitted diseases in the world. A naturally occurring variation of the terminal carbohydrates on the lipooligosaccharide (LOS) molecule correlates with altered disease states. Here, we investigated the interaction of different stable gonoccocal LOS phenotypes with human dendritic cells and demonstrate that each variant targets a different set of receptors on the dendritic cell, including the C-type lectins MGL and DC-SIGN.

Identification of a novel lipopolysaccharide core biosynthesis gene cluster in Bordetella pertussis, and influence of core structure and lipid A glucosamine substitution on endotoxic activity.

Lipopolysaccharide (LPS), also known as endotoxin, is one of the main constituents of the gram-negative bacterial outer membrane. Whereas the lipid A portion of LPS is generally considered the main determinant for endotoxic activity, the oligosaccharide moiety plays an important role in immune evasion and the interaction with professional antigen-presenting cells. Here we describe a novel four-gene cluster involved in the biosynthesis of the Bordetella pertussis core oligosaccharide.

Differential activation of human and mouse Toll-like receptor 4 by the adjuvant candidate LpxL1 of Neisseria meningitidis.

Neisseria meningitidis LpxL1 lipopolysaccharide (LPS) bearing penta-acylated lipid A is considered a promising adjuvant candidate for inclusion in future N. meningitidis vaccines, as it elicits a markedly reduced endotoxic response in human macrophages relative to that in wild-type (hexa-acylated) LPS, while it is an equally effective adjuvant in mice. As dendritic cells (DC) and Toll-like receptors (TLR) are regarded as central mediators in the initiation of an immune response, here we evaluated the ability of LpxL1 LPS to mature and to activate human DC and examined its TLR4-/MD-2-activating properties.

A critical contribution of both CD28 and ICOS in the adjuvant activity of Neisseria meningitidis H44/76 LPS and lpxL1 LPS.

The development of novel vaccines against Neisseria meningitidis recently gained momentum by the generation of penta-acylated lpxL1 LPS which has similar adjuvant activity, but reduced endotoxic activity as compared to hexa-acylated wild type (H44/76) LPS. We investigated the costimulation requirements for the adjuvant activity of both forms of LPS by immunizing CD28-, ICOS- and B7.1/2/ICOS-deficient mice.