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

脑膜炎奈瑟菌定植于人鼻咽部，在儿童和青少年时期偶尔引起严重的侵袭性疾病。在过去的几十年中，已经阐明了脑膜炎球菌用于宿主适应和免疫逃避的各种分子机制。在这个应用程序中，我们将调查生物膜和外膜囊泡的作用，以前被忽视的形态结构可能参与病原体宿主相互作用和免疫逃避。基于我们发表的生物膜工作，我们将研究生物膜分离过程，我们认为这是必不可少的宿主内传播和宿主间传播。我们将着重研究菌毛器的动态表达。此外，我们将测试的假设，即分离阶段不同的所谓的定居者和扩展株，我们最近提出的脑膜炎球菌的两个基本生活方式。在准备工作中，我们最近收集了令人信服的证据，脑膜炎球菌外膜囊泡干扰中性粒细胞效应机制。因此，我们将研究外膜水泡对免疫逃避策略的影响背后的分子机制。滤过泡介导的血清补体攻击的避免、中性粒细胞的沉默以及通过滤过泡释放的中性粒细胞胞外陷阱的逃逸将是研究的焦点。

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.