| Moraxella catarrhalis, a gram-negative mucosal pathogen, is the third most common cause of bacterial infections associated with otitis media in children and exacerbations in patients with chronic obstructive pulmonary disease (COPD). A major component of the outer membrane of these bacteria is the glycolipid, termed lipooligosaccharide (LOS). In M. catarrhalis , LOS consists of a lipid A molecule attached to a di-KDO molecule linked to a series of branched hexose sugar residues. M. catarrhalis can be divided into three serotypes based on the LOS structure that the strain expresses. A majority of clinical isolates express either serotype A or serotype B LOS, while very few isolates express serotype C. Little is known about the synthesis and addition of sugar residues of these complex molecules, in addition to the relevance these molecules have during infection. The LOS expressed by Haemophilus influenzae and Neisseria species has been shown to be important in infection and these biologically active glycolipids share some similar epitopes to M. catarrhalis LOS. To begin to ascertain if individual carbohydrate residues and substitutions of M. catarrhalis LOS are important in various steps of pathogenesis, the biosynthesis of the LOS molecule must be understood. This study identified the full set of LOS glycosyltransferases (lgt ) responsible for constructing the LOS molecule for each serotype. There were six genes identified that are required for the various LOS serotype structures, in addition to multiple alleles. Mutations in each gene encoding these glycosyltransferases resulted in a specifically truncated LOS structure. These truncated structures were used to analyze the human serum antibody response to various LOS epitopes developed in COPD patients that experience an exacerbation induced by a M. catarrhalis infection. New human antibodies were detected in a set of patients to both serotype specific structures and various internal and terminal oligosaccharide epitopes. To better understand the disproportion of LOS serotypes isolated in the clinical setting, a strain that is capable of expressing each serotype individually was constructed to begin to dissect why serotype A and B strains appear much better suited for colonization or infection in the human host. This study has allowed a better understanding of the assembly of the M. catarrhalis LOS molecule in order to learn the role of LOS in the human host. |
