Type IV pilus as a switch that determines consequences of Neisseria colonization

IV 型菌毛作为决定奈瑟菌定植后果的开关

• 批准号: 8589225
• 负责人: MAGDALENE Y SO
• 金额: $ 51.65万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-08 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8589225
• 关键词: Address; Animal Model; Area; Bacteria; Behavior; Biogenesis; Biology; Blood; Cell Communication; Cells; Cellular Structures; Collaborations; Destinations; Epithelial Cells; Event; Fiber; Genes; Genetic Transcription; Genitourinary system; Goals; Human; Infection; Inflammatory Response; Integration Host Factors; Iron; Label; Location; Mediating; Motor; Neisseria; Outcome; Oxygen; Pathogenesis; Pharyngeal structure; Pilum; Proteins; Proteomics; Railroads; Recruitment Activity; Reporting; Role; Sigma Factor; Signal Pathway; Signal Transduction; Signaling Protein; Speed; Structure; Surface; Symbiosis; Testing; Training; Transcriptional Regulation; Virulence Factors; cell cortex; college; in vivo; pathogen; response; trafficking

DESCRIPTION (provided by applicant): The Type IV pilus (Tfp) is a virulence factor that mediates the initial contact of pathogenic Neisseria with epithelial cells. It subsequently activates signaling pathways that modulate cellular responses to infection. Attachment is mediated by static Tfp fibers. Signaling requires physical force exerted on the colonized cell by retracting fibers. Our preliminary findings indicate Tfp of commensal Neisseria also mediates attachment. However, the biology of commensal and pathogenic Neisseria Tfp differs in two major respects. 1) Tfp genes encoding the attachment and retraction components are under different transcriptional regulation. 2) Tfp retraction activates different signaling cascades in te epithelial cell. We hypothesize Tfp is a switch that determines whether Neisseria colonization leads to commensalism (asymptomatic colonization) or pathogenesis. This is analogous to a railroad switch at a junction that directs a train (bacterium) down tracks leading to different destinations (commensalism or pathogenesis). We further hypothesize the Tfp switching mechanism consists of two critical components: transcriptional regulation of its machinery genes, and its epithelial cell signaling activities. Transcriptional regulation determines when and where Tfp-mediated attachment and retraction occur. The types of signaling cascades activated in the host cell determine the outcome of colonization. We propose two Aims to test this hypothesis.

描述（由申请人提供）：IV型菌毛（TFP）是一种毒力因子，可介导致病性奈瑟氏菌与上皮细胞的初始接触。随后，它激活了调节感染细胞反应的信号通路。附件由静态TFP纤维介导。信号传导需要通过缩回纤维在定殖细胞上施加的物理力。我们的初步发现表明，共生奈瑟氏菌的TFP也介导了附着。然而，在两个主要方面，共生和致病性奈瑟氏菌TFP的生物学有所不同。 1）编码附件和缩回成分的TFP基因在不同的转录调控下。 2）TFP回缩激活上皮细胞中的不同信号级联。我们假设TFP是确定奈瑟氏菌定殖的开关，是导致共识（无症状定植）还是发病机理。这类似于连接处的铁路开关，该连接指导火车（细菌）沿着导致不同目的地的轨道（共同主义或发病机理）。我们进一步假设TFP切换机制由两个关键组成部分组成：其机械基因的转录调控及其上皮细胞信号传导活性。转录调节确定何时和 发生TFP介导的附着和缩回的地方。在宿主细胞中激活的信号级联反应的类型决定了定殖的结果。我们提出了两个目的来检验这一假设。