Moraxella catarrhalis Lipooligosaccharide - a Journey of Assembly and Structure

Abstract

Moraxella catarrhalis is a human pathogen that causes serious diseases such as otitis media in children and lower respiratory ailments such as chronic obstructive pulmonary disease (COPD) in the elderly. M. catarrhalis produces a surface-embedded lipooligosaccharide (LOS) that is composed of lipid A and oligosaccharide. Lipid A constitutes the outer-membrane embedded hydrophobic component of the LOS and is responsible for its endotoxic activity, while the oligosaccharide is usually highly hydrophilic in nature. There are presently three major serotypes of M. catarrhalis, A, B and C, which have differing oligosaccharide profiles in their LOS, along with varying antigenic responses. The oligosaccharide components of these serotypes has been structurally characterised previously. Several studies, including our own have generated and used truncated forms of the oligosaccharide to understand how the glycosyltransferase enzymes responsible for the biosynthesis of the oligosaccharide function in this biosynthetic process. As part of our ongoing interest in understanding the assembly of both the oligosaccharide and lipid A portions of the LOS for the development of therapeutic agents, we have investigated the lipid A structure of a serotype B glycosyltransferase mutant LOS. Of note, the lipid A or endotoxin of serotype A wild type M. catarrhalis has previously been characterised. The resulting oligosaccharide was highly truncated as expected, however of particular interest was that the lipid A phosphorylation and fatty acyl chain substitution pattern of this mutant differs from that previously reported for serotype A wild type M. catarrhalis. The work that has gone into understanding the glycosyltransferase assembly and structure of the oligosaccharide (LOS-derived) of M. catarrhalis, plus the interesting variation in lipid A structure that we have observed for the serotype B lgt3? mutant are reviewed in this paper.