Characterisation of surface traits of Helicobacter pylori and their role in the infectious process

• The surface appendages of bacteria determine the initial contact with host cells. Characterisation of functional organisation and spatial distribution of adhesive traits of outer membrane components of Gram-negative bacteria is a key issue in studies of the parasite-host cell interaction.With focus on the enteropathogenic Helicobacter pylori, evidenced to cause chronic gastric infections in humans, detergent-digested freeze fracture replica labelling was applied for ultrastructural analyses of envelope distribution of the virulence factors blood group antigen binding adhesin (BabA), and the carbonic anhydrases (α-CA, ß-CA). In a preliminary study the methodology was also used to study the bacteria-host contact between phagocytosing human neutrophils and wild-type H. pylori.In parallel, bacterial traits were analysed from a molecular and biochemical perspective. This included the specific roles of the BabA and the sialic acid-binding adhesin (SabA), and the neutrophil activating protein (HP-NAP) in neutrophilic stimulation and subsequent inflammatory process. It was concluded that SabA is crucial in the initiation of a neutrophilic response in the mediated inflammation.This thesis has demonstrated the synergistic application of ultrastructural, molecular and cellular microbiology tools for delineating complex patterns in bacteria-host interactions, thus utilising the well-characterised and clinically important human pathogen H. pylori. This approach could be applicable to other Gram-negative species to clarify known and discern new virulence mechanisms in the multifaceted field of bacterial pathogenesis and bacterial interactions with human host cells.

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MEDICINE

MEDICIN

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