Host-dependent pathogenicity and phasevarions in human airway pathogens

Non-typeable Haemophilus influenzae (NTHi) is a commensal and relatively harmless in the nasopharynx. However, it occasionally also causes acute otitis media (AOM) in preschool children and pneumonia/ bronchitis, particularly in patients with chronic obstructive pulmonary disease (COPD). The Riesbeck research team aims to investigate the complex virulence mechanisms of NTHi with the long-term goal to define new antimicrobial treatment strategies. We want to characterize previously undescribed mechanisms that regulate the phase variation of H. influenzae involved in opportunistic interactions with the host during inflammation that ultimately can lead to bacterial persistence. The project mainly evaluates the phase variation in bacterial blebbing (release of extracellular outer membrane vesicles) as well as characterization of the mechanisms of H. influenzae for secretion of extracellular vesicles with different components and sizes. On top of the above, the Riesbeck team also further focuses on the engineering of a modern vaccine against AOM so that vesicles can be used to deliver newly characterized Haemophilus virulence factors as vaccine components. The prophylactic effects of this engineered vaccine against NTHi-related AOM are to be tested and evaluated in transgenic animal models. In concordance with the emergence of antimicrobial resistance in Gram-negative bacterial pathogens, the research project conducting in the laboratory will be the impetus for a therapeutic platform applicable to several bacteria.