Invited review: Profiling structural elements of short-chain lipopolysaccharide of non-typeable Haemophilus influenzae

Abstract

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. The chemical composition of non-typeable Haemophilus influenzae (NTHi) LPS is highly diverse. It contains a number of different monosaccharides (Neu5Ac, L-glycero-D-manno heptose, D-glycero-D-manno heptose, Kdo, D-Glc, D-Gal, D-GlcNAc, D-GalNAc) and non-carbohydrate substituents. Prominent non-carbohydrate components are O-acetyl groups, glycine and phosphates. We now know that sialic acid (N-acetylneuraminic acid or Neu5Ac) and certain oligosaccharide extensions are important in the pathogenesis of NTHi; however, the biological implications for many of the various features are still unknown. Electrospray ionization mass spectrometry in combination with separation techniques like CE and HPLC is an indispensable tool in profiling glycoform populations in heterogeneous LPS samples. Mass spectrometry is characterized by its extreme sensitivity. Trace amounts of glycoforms expressing important virulence determinants can be detected and characterized on minute amounts of material. The present review focuses on LPS structures and mass spectrometric methods which enable us to profile these in complex mixtures.

NMR-based Structural Analysis of the Complete Rough-type Lipopolysaccharide Isolated from Capnocytophaga canimorsus

“…It is also found in core oligosaccharides from other Gram-negative bacteria, such as Haemophilus influenzae I-69 (40) and in non-typeable H. influenzae, where this position of Kdo carries a pyrophosphoethanolamine residue (41). Additionally, such phosphorylation has been identified in the inner core oligosaccharide of Bordetella pertussis (42) and Vibrio cholerae (43).…”

Divergent Pro-Inflammatory Profile of Human Dendritic Cells in Response to Commensal and Pathogenic Bacteria Associated with the Airway Microbiota

“…However, some Gram-negative bacteria are reported to contain less potent atypical LPS composed of lipid A with shorter or fewer acyl chains [39]–[41]. LPS derived from Haemophillus influenzae and Moraxella catarrhalis has been reported to contain hexa- and hepta-acylated lipid A, respectively [42], [43]. No studies have been reported on LPS of the Prevotella or Veillonella species included in our study; yet LPS from other species within these genera have been analyzed.…”

Shielding of a Lipooligosaccharide IgM Epitope Allows Evasion of Neutrophil-Mediated Killing of an Invasive Strain of Nontypeable Haemophilus influenzae

“…Whereas incorporation of a galactose on HepIII is considered to be a terminal moiety, glucose on HepIII can be substituted with galactose depending on lic2A gene activity (19), which is controlled by phase variation, a mechanism that switches translation of genes on or off (39). Phase-variable on-off translation of genes is a stochastic process dependent on slipped-strand mispairing of tandem repeats present in the gene, which occurs with a high frequency (10 −2 to 10 −3 times per generation) and leads to switching the coding region in or out of frame.…”

“…In addition, variation and modifications in its lipooligosaccharide (LOS) composition have been shown to prevent complement activation (15–18). The LOS structure of NTHi consists of three parts: (i) lipid A, (ii) an inner core comprised of a single 3-deoxy- d -manno-octulosonic acid (Kdo) linked to three conserved heptoses (Hep), and (iii) an outer core containing variable oligosaccharide extensions (19). Specific LOS structures have been shown to prevent binding of antibody and complement factor C4b, which increases their resistance to complement-mediated lysis (15, 16).…”