The role of Moraxella catarrhalis outer membrane proteins in pathogenesis

Detta är en avhandling från Dept of Laboratory Medicine, Medical Microbiology, Malmö

Sammanfattning: Moraxella catarrhalis is an important respiratory pathogen. It is a common cause of otitis media in children, a usual infections agent in sinusitis and makes up to 10% of all exacerbations of chronic obstructive pulmonary disease (COPD). It is known to cause more frequent disease in the colder season, and, generally, its importance is recognised mainly in countries exposed to moderate climate. M. catarrhalis widely colonises infants and children but it is very uncommon for the bacterium to colonise the mucosa in adults. The present thesis is concentrated on discussing two properties of M. catarrhalis, - binding and inactivation of alpha1-anticnymotrypsin (ACT) and complement component 3 (C3) for which M. catarrhalis outer membrane proteins “ubiquitous surface proteins” (Usp) A1/A2 are responsible. No other pathogenic bacterium is known to bind ACT. The ACT is a serine protease inhibitor playing important part in antiprotease lung protection and anti-inflammatory signalling. We established that M. catarrhalis is able to bind and inactivate ACT through the two active domains on both UspA1 and A2 proteins. The phenomenon is proposed to be important for a) protease-antiprotease balance in the lung, for b) exacerbating inflammation and for c) inhibition of phagocytic clearance of M. catarrhalis. The localization of ACT binding inside the UspA1 and A2 proteins provided us with means to develop a simple and quick method for purification of ACT from plasma or serum based on ACT affinity to a fragment of UspA2 protein of M. catarrhalis. The purification can be carried out practically in one step and the biological properties of ACT are retained. In the last part of the thesis the C3 binding to M. catarrhalis Usp A1 and A2 was studied. The binding has been attributed to a single fragment in the both UspA1 and A2. Importantly, C3d fragment of C3 has been found responsible for the binding to UspA1/A2. The UspA2 has been demonstrated to inhibit both the classical and the alternative pathways of the complement. The C3 binding by M. catarrhalis strongly correlated with serum resistance of the bacterium, as well as with the expression of UspA1/A2.

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