Neisseria genes required for persistence identified via in vivo screening of a transposon mutant library.
Neisseria genes required for persistence identified via in vivo screening of a transposon mutant library.
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DOI：
10.1371/journal.ppat.1010497
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发表时间：
2022-05
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
--
作者：
人类适应性肠道奈瑟氏菌在其宿主中形成和维持生态位的机制尚不清楚。这些微生物是粘膜微生物群的常见成员，与脑膜炎奈瑟菌和淋病奈瑟菌共享许多推定的宿主相互作用因子。评估这些共享因素在宿主携带过程中的作用，可能会提供深入了解细菌的机制，驱动整个属的寄生虫和无症状感染。我们确定了宿主的相互作用所需的生态位的发展和维护，通过在体内筛选的转座子突变库的Neisseria musculi，一个持久的和无症状的殖民地的口腔和肠道的CAST/EiJ和A/J小鼠的野生捕获的小鼠的寄生虫。大约500个候选基因参与长期宿主相互作用被确定。这些包括假定的N的同系物。脑膜炎和脑膜炎奈瑟氏球菌（N.淋病毒力因子，其已显示在体外调节宿主相互作用。重要的是，许多候选基因没有指定的功能，说明有多少仍然是了解奈瑟菌的持久性。许多功能未知的基因在人类适应的奈瑟氏菌属物种中是保守的;它们可能为理解致病性和寄生性奈瑟氏菌在其天然宿主中建立和维持生态位的机制提供途径。候选基因的一个子集的验证证实了多糖胶囊在N。肌肉持久性，但不是殖民化。我们的研究结果突出了肌奈瑟氏菌-小鼠模型作为研究致病性奈瑟氏菌的工具的潜在效用;我们的工作代表了鉴定跨属保守的新型宿主相互作用因子的第一步。奈瑟氏菌属包含许多动物和人类的遗传相关病原体，以及两种人类病原体，淋病奈瑟氏菌和脑膜炎奈瑟氏菌。但对奈瑟氏球菌在宿主中维持生态位的机制知之甚少。为了确定持久性所需的基因，我们筛选了一个转座子突变体的库，肌肉奈瑟氏球菌，野生捕获的小鼠，在CAST/EiJ小鼠，持续和无症状的殖民。大约500个候选宿主相互作用基因被确定。其中的一个子集是N的同系物。脑膜炎和脑膜炎奈瑟氏球菌（N.已知在体外调节病原体-宿主相互作用的淋病基因。许多候选基因没有已知的功能，这表明关于N还有很多东西需要了解。肌龛维持。由于许多功能未知的基因在人类适应性奈瑟氏菌中是保守的，它们为理解奈瑟氏菌的持久性机制提供了一个途径。
The mechanisms used by human adapted commensal Neisseria to shape and maintain a niche in their host are poorly defined. These organisms are common members of the mucosal microbiota and share many putative host interaction factors with Neisseria meningitidis and Neisseria gonorrhoeae. Evaluating the role of these shared factors during host carriage may provide insight into bacterial mechanisms driving both commensalism and asymptomatic infection across the genus. We identified host interaction factors required for niche development and maintenance through in vivo screening of a transposon mutant library of Neisseria musculi, a commensal of wild-caught mice which persistently and asymptomatically colonizes the oral cavity and gut of CAST/EiJ and A/J mice. Approximately 500 candidate genes involved in long-term host interaction were identified. These included homologs of putative N. meningitidis and N. gonorrhoeae virulence factors which have been shown to modulate host interactions in vitro. Importantly, many candidate genes have no assigned function, illustrating how much remains to be learned about Neisseria persistence. Many genes of unknown function are conserved in human adapted Neisseria species; they are likely to provide a gateway for understanding the mechanisms allowing pathogenic and commensal Neisseria to establish and maintain a niche in their natural hosts. Validation of a subset of candidate genes confirmed a role for a polysaccharide capsule in N. musculi persistence but not colonization. Our findings highlight the potential utility of the Neisseria musculi-mouse model as a tool for studying the pathogenic Neisseria; our work represents a first step towards the identification of novel host interaction factors conserved across the genus. The Neisseria genus contains many genetically related commensals of animals and humans, and two human pathogens, Neisseria gonorrhoeae and Neisseria meningitidis. The mechanisms allowing commensal Neisseria to maintain a niche in their host is little understood. To identify genes required for persistence, we screened a library of transposon mutants of Neisseria musculi, a commensal of wild-caught mice, in CAST/EiJ mice, which persistently and asymptomatically colonizes. Approximately 500 candidate host interaction genes were identified. A subset of these are homologs of N. meningitidis and N. gonorrhoeae genes known to modulate pathogen-host interactions in vitro. Many candidate genes have no known function, demonstrating how much remains to be learned about N. musculi niche maintenance. As many genes of unknown function are conserved in human adapted Neisseria, they provide a gateway for understanding Neisseria persistence mechanisms in general.
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影响因子：
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作者：
Dillard JP
通讯作者：
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影响因子：
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