The Neisseria Type IV pilus as a mediator of persistent colonization

项目总结 持久定植是微生物-宿主相互作用的一个关键方面。鲜为人知 关于允许细菌持久地在宿主上定居的机制。我们有 开发了一种小鼠模型，用于解剖持久性肺炎的细菌和宿主决定因素 殖民主义。它将野生小鼠的共生体肌肉奈瑟氏菌与实验室小鼠配对， 它并不是自然地被奈瑟里亚殖民的。肌动杆菌与其密切相关 奈瑟氏菌的共生种和致病种，并编码许多宿主相互作用 这些病原体的影响因素和疫苗候选。单剂口服肌动杆菌 导致小鼠口腔和肠道持续无症状的定植 至少1年。定植不仅需要IV型菌毛(TFP)纤维，还需要 纤维的回缩。不表达菌毛纤维亚基和Δ菌毛的Δ桩， 其中不表达毛发收缩马达，两者都不能定植小鼠。在这里，我们 将使用我们新开发的模型来检查TFP回缩对N.肌肉的作用 殖民主义和坚持不懈。我们还将使用光谱成像荧光原位 用杂交(FISH)技术定位和鉴定肌动杆菌及其所形成的生物膜 TFP在小鼠消化道中的回缩突变。

PROJECT SUMMARY Persistent colonization is a key facet of microbe-host interactions. Little is known about the mechanisms that allow a bacterium to persistently colonize its host. We have developed a mouse model for dissecting bacterial and host determinants of persistent colonization. It pairs a commensal of wild mice, Neisseria musculi, with the lab mouse, which is not naturally colonized with Neisseria. N. musculi is closely related to commensal and pathogenic species of Neisseria, and encode many host interaction factors and vaccine candidates of these pathogens. A single oral dose of N. musculi results in persistent, asymptomatic colonization of the oral cavity and gut of the mouse for at least 1 year. Colonization requires not only the Type IV pilus (Tfp) fiber but also retraction of the fiber. ΔpilE, which does not express the pilus fiber subunit and ΔpilT, which does not express the pilus retraction motor, both fail to colonize mice. Here, we will use our newly developed model to examine the role of Tfp retraction on N. musculi colonization and persistence. We will also use spectral imaging Fluorescence In Situ Hybridization (FISH) to locate and characterize the biofilms formed by N. musculi and its Tfp retraction mutant in the mouse alimentary tract.