Expression and structural diversity of the lipopolysaccharide of Haemophilus influenzae: implication in virulence

Lipopolysaccharide (LPS) is a major virulence determinant of the human bacterial pathogen Haemophilus influenzae. A characteristic feature of H. influenzae LPS is the extensive intra- and inter-strain heterogeneity of glycoform structure which is key to the role of the molecule in both commensal and disease-causing behaviour of the bacterium. Through the combination of genetics and detailed structural analyses, H. influenzae is an exemplar Gram-negative bacterium for which now the most extensive and detailed LPS structural data and functional correlates are available. LPS from H. influenzae consists of a conserved glucose-substituted triheptosyl inner-core moiety l-alpha-d-Hepp-(1-->2)-[PEtn-->6]-l-alpha-d-Hepp-(1-->3)-[beta-d-Glcp-(1-->4)]-l-alpha-d-Hepp linked to lipid A via Kdo 4-phosphate. The inner-core unit provides the template for attachment of oligosaccharide- and non-carbohydrate substituents. Here, the structure, genetics and expression of LPS glycoforms in the outer core are reviewed as well as their implication on virulence.