Analysis of the biosynthesis and function of a serotype B glycoform of Moraxella catarrhalis lipooligosaccharides
Edwards, Katie J
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Moraxella catarrhalis is an important human pathogen and a major cause of otitis media in children and respiratory infection in adults with chronic obstructive pulmonary disease (COPD). Few virulence factors have been characterized for M. catarrhalis ; however these bacteria express lipooligosaccharide (LOS) molecules, which share epitopes similar to that of the Neisseria and Haemophilus species. More importantly, these common LOS epitopes have been implicated in various steps of pathogenesis for the different organisms. Although preliminary reports have described M. catarrhalis LOS structure, the steps involved in LOS biosynthesis remain poorly defined. These studies have characterized the specific function of three glycosyltransferase enzymes (Lgt1, Lgt2, and Lgt3) shown to be essential for the biosynthesis of the serotype B LOS expressed by M. catarrhalis 7169. This work has also revealed the Lgt3 enzyme as the first multifunctional glucosyltransferase involved in the biosynthesis of an LOS molecule, as it is essential for the addition of alternately linked glucose molecules onto this major glycoform. Structural and serological studies have described three LOS serotypes (A, B, and C), differing in length and content of the oligosaccharide branches. Serological determinations of M. catarrhalis LOS expression are complicated by the limited quantities of antibodies and the cross-reactivity between serotypes A and C. These studies have identified a genetic locus of glycosyltransferase genes that differentiates between the three serotypes using a multiplex PCR assay. We have used this tool to determine the LOS type expressed by M. catarrhalis strains clinical isolates from COPD patients and children with otitis media. Our results were consistent with previous studies as serotype A LOS were the most prevalent, followed by serotype B and serotype C, however they also suggest that the extent of this serotypic variation may be limited when analyzing a geographically restricted population. In addition, we have analyzed pre-acquisition and post-clearance samples from COPD patients for development of LOS antibodies. These studies suggest that these patients may develop new IgG antibodies to M. catarrhalis LOS, and some patients develop antibodies directed to the homologous LOS, whereas others developed cross-reactive antibodies to all serotypes. Overall these studies have furthered the knowledge of M. catarrhalis LOS biosynthesis, as well as provided insight to the role of this important molecule in the human immune response.