A Natural Mouse Model for Neisseria Colonization.

A Natural Mouse Model for Neisseria Colonization.
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DOI:
10.1128/iai.00839-17
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发表时间:
2018-05
影响因子:
3.1
通讯作者:
So M
So M
中科院分区:
医学2区
文献类型:
--
作者:
Ma M;Powell DA;Weyand NJ;Rhodes KA;Rendón MA;Frelinger JA;So M

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共生体对多细胞生物的正常功能至关重要。共生体是如何建立对宿主的持久殖民的,人们知之甚少。由于缺乏动物模型,对微生物-宿主相互作用这方面的研究受到阻碍。我们已经开发了一种天然的小动物模型,用于识别宿主和共栖决定因素的定植和难以捉摸的持久性过程。我们的系统将野生小鼠的一种共生细菌肌肉奈瑟菌与实验室小鼠配对。与自然寄主共生的小鼠配对可以避免寄主限制问题。研究是在没有抗生素、激素、侵入性手术或对宿主进行基因操作的情况下进行的。口服单剂量的肌肉乳杆菌可导致口腔和肠道的长期定植。所有的老鼠都很健康。对定植的易感性是由宿主遗传和先天免疫决定的。对于肌肉奈瑟菌来说,定植需要IV型菌毛。试剂和强大的工具很容易用于操纵实验室小鼠,允许轻松解剖控制定植抗性的宿主决定因素。肌肉奈瑟菌与人类居住的共生和致病性奈瑟菌有遗传关系,并编码致病性奈瑟菌的宿主相互作用因子和疫苗抗原。我们的系统为研究奈瑟菌与宿主的相互作用提供了一种自然的方法,并可能对疫苗功效研究有用。
Commensals are important for the proper functioning of multicellular organisms. How a commensal establishes persistent colonization of its host is little understood. Studies of this aspect of microbe-host interactions are impeded by the absence of an animal model. We have developed a natural small animal model for identifying host and commensal determinants of colonization and of the elusive process of persistence. Our system couples a commensal bacterium of wild mice, Neisseria musculi, with the laboratory mouse. The pairing of a mouse commensal with its natural host circumvents issues of host restriction. Studies are performed in the absence of antibiotics, hormones, invasive procedures, or genetic manipulation of the host. A single dose of N. musculi, administered orally, leads to long-term colonization of the oral cavity and gut. All mice are healthy. Susceptibility to colonization is determined by host genetics and innate immunity. For N. musculi, colonization requires the type IV pilus. Reagents and powerful tools are readily available for manipulating the laboratory mouse, allowing easy dissection of host determinants controlling colonization resistance. N. musculi is genetically related to human-dwelling commensal and pathogenic Neisseria and encodes host interaction factors and vaccine antigens of pathogenic Neisseria. Our system provides a natural approach for studying Neisseria-host interactions and is potentially useful for vaccine efficacy studies.