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The Neisseria Type IV pilus as a mediator of persistent colonization

IV 型奈瑟菌菌毛作为持续定植的介质

基本信息

批准号：
9884734
负责人：
MAGDALENE Y SO
金额：
$ 19.29万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-05 至 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9884734
关键词：
ATP phosphohydrolase Animal Model Animals Antibiotics Bacteria Behavior Biological Collaborations Defect Development Disease Dose Event Fiber Fluorescent in Situ Hybridization Foundations Frequencies Future Gastrointestinal tract structure Genome Goals Hormones Human Hybrids In Situ In Vitro Infection Innate Immune System Laboratories Light Link Logistics Macaca mulatta Maintenance Mediating Mediator of activation protein Microbe Microbial Biofilms Modeling Motor Mus Neisseria Neisseria gonorrhoeae Neisseria meningitidis Operative Surgical Procedures Oral Oral cavity Pathogenicity Phenotype Pilum Procedures Proteins Public Health Reporting Research Personnel Resources Role Signal Transduction Site Structure Study models System Techniques Technology Testing Time Tissues Vaccines Wood material antimicrobial chronic infection fluorescence imaging genetic manipulation host-microbe interactions in vivo man member microbial community microbiota mouse model mutant novel pathogen spectrograph tissue/cell culture tool development vaccine candidate vaccine development

项目摘要

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.

项目摘要持续定植是微生物-宿主相互作用的一个关键方面。知之甚少关于细菌在宿主体内持续繁殖的机制我们有开发了一种小鼠模型，用于解剖细菌和宿主决定因素，殖民化它将一群野生小鼠，肌肉奈瑟氏菌，与实验室小鼠配对，它不是奈瑟氏菌的天然定植地。N.肌肉与奈瑟氏菌属的寄生和致病种，并编码许多宿主相互作用这些病原体的因子和疫苗候选物。单次口服N.肌导致小鼠口腔和肠道的持续的、无症状的定植至少1年。定植不仅需要IV型菌毛（Tfp）纤维，纤维的收缩。ΔpilE不表达菌毛纤维亚单位和ΔpilT，其不表达菌毛回缩马达，两者都不能定殖小鼠。这里我们将使用我们新开发的模型来研究Tfp收缩对N的作用。肌殖民化和持久性。我们还将使用光谱成像荧光原位杂交（FISH）定位和表征N。肌肉及其小鼠消化道内Tfp收缩突变体。