Mechanisms of host adaptation and immune evasion of Neisseria meningitidis: the role of biofilms and blebs

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Neisseria meningitidis colonizes the human nasopharynx and sporadically causes severe invasive disease in childhood and adolescence. In the past decades, a variety of molecular mechanisms have been elucidated that are employed by meningococci for host adaptation and immune evasion. In this application, we will investigate the role of biofilms and outer membrane vesicles as previously neglected morphological structures possibly involved in pathogen host interaction and immune evasion. Based on our published work on biofilms, we will study biofilm detachment processes, which we think are essential for within-host spread and between-host transmission. We will focus on the investigation of dynamic expression of the pilus apparatus. Furthermore, we will test the hypothesis that the detachment phase differs in the so-called settler and spreader strains, which we recently proposed as two basic lifestyles of meningococci. In preparatory work we recently collected convincing evidence that meningococcal outer membrane vesicles interfere with neutrophil effector mechanisms. We will therefore study the molecular mechanisms behind the effect of outer membrane blebs on immune evasion strategies. Bleb mediated avoidance of serum complement attack, silencing of neutrophils, and escape of neutrophil extracellular traps by bleb release will be focus of the investigations.