Structural studies of lipopolysaccharides expressed by non-typeable Haemophilus influenzae and Haemophilus parainfluenzae strains

The present thesis describes lipopolysaccharide (LPS) structures expressed by non-typeable Haemophilus influenzae and Haemophilus parainfluenzae strains. LPS is a major surface component of Gram-negative bacteria. Structural studies of LPS are very important for understanding the adaptive mechanisms which help bacteria to survive in the host environment.

Non-typeable Haemophilus influenzae (NTHi) is a common human commensal of the nasopharynx. It is also pathogenic and causes both acute and chronic diseases, such as otitis media, sinusitis, pneumonia and bronchitis. H. influenzae expresses rough type LPS (lacking O-antigen), which is implicated as a major virulence factor. 25 NTHi otitis media isolates were selected for structural studies of LPS. These clinical isolates represent the structural diversity of LPS in the natural population.

Structural studies of H. influenzae LPS have resulted in a molecular model consisting of a conserved (PEtn)-substituted triheptosyl inner-core moiety (HepI–HepII-HepIII) in which each of the heptose residues can provide a point for elongation by oligosaccharide chains (outer-core region).

NTHi strains 1158/1159 and 1232, described in this thesis, were selected from this collection of clinical isolates. These strains express additional D,D-Hep residue in the outer-core region of LPS.

Haemophilus parainfluenzae is a part of normal human flora. Previous studies have indicated that H. parainfluenzae expresses LPS structures that are very similar to those expressed by H. influenzae. On the other hand some H. parainfluenzae strains express O-antigen containing LPS. The structures of the O-antigen from H. parainfluenzae strains 20 and 16 are described in this thesis.

The structural investigations of LPS of H. influenzae and the comparison with LPS expressed by H. parainfluenzae will increase the knowledge of biological properties of LPS and its role in bacterial virulence.

List of scientific papers

I. The structural diversity of lipopolysaccharide expressed by non-typeable Haemophilus influenzae strains 1158 and 1159. Vitiazeva, V., Li, J., Hood, D. W., Richard Moxon, E., and Schweda, E. K. (2012) Carbohydrate research. 357, 98-110.
https://doi.org/10.1016/j.carres.2012.04.023

II. The structural studies of a novel branching pattern in the lipopolysaccharide expressed by non-typeable Haemophilus influenzae strain 1232. Vitiazeva, V., Månsson, M., Li, J., Hood, D. W., Richard Moxon, E., and Schweda, E. K. [Manuscript]

III. Structural studies of the lipopolysaccharide from Haemophilus parainfluenzae strain 20. Vitiazeva, V., Twelkmeyer, B., Young, R., Hood, D. W., and Schweda, E. K. (2011) Carbohydrate research. 346, 2228-2236.
https://doi.org/10.1016/j.carres.2011.07.006

IV. Structural studies of the O-antigen from Haemophilus parainfluenzae strain 16. Vitiazeva, V., Young, R., Hood, D. W., and Schweda, E. K. [Manuscript]