Studies into the Genetic Diversity and Complement Resistance Phenotype of Moraxella catarrhalis

The aim of this thesis was to help define the contribution of Moraxella catarrhalis genetic diversity on the ability of the bacterium to colonise and cause infection in the human host, as well as to investigate novel genes/mechanisms associated with isolates exhibiting the complement resistance phenotype. In this respect, we show that M. catarrhalis is a genetically diverse organism in hospitalised children, with type-switching not leading to an increase in disease burden. Further, vaccination with a Streptococcus pneumoniae vaccine (an organism that shares the same biological niche as M. catarrhalis) does not affect M. catarrhalis diversity. Finally, genetically diverse isolates were found within otitis media-prone children, as well as a low frequency of intra-genomic variation in two complement resistance associated genes. With respect to genes/mechanisms associated with the complement phenotype, a novel major outer membrane protein of M. catarrhalis (OMP J) associated (but not conferring) complement resistance was identified and characterised. This protein existed in two major forms, was immunogenic, but was found not to be a suitable vaccine candidate. In a further study, both complement resistant and complement sensitive isolates of M. catarrhalis were found to be only weak activators of the mannose-binding lectin (MBL) pathway of complement activation (a useful survival strategy). Finally, a novel plasmid of M. catarrhalis is described named pEMCJH03 (and only the second plasmid to be identified within this species). This plasmid may be useful as a cloning and expression vector for putative M. catarrhalis virulence genes (including the testing of complement resistance-associated genes).

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