Bacterial cell envelope in polar positioning of autotransporter proteins

自转运蛋白极性定位中的细菌细胞包膜

• 批准号: 8638264
• 负责人: Marcia B Goldberg
• 金额: $ 21.75万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8638264
• 关键词: Actins; Adhesions; Attenuated; Bacteria; Bacterial Genome; Bacterial Infections; Bacterial Proteins; Bordetella pertussis; Cell division; Cell membrane; Cell physiology; Cells; Cellular biology; Centers for Disease Control and Prevention (U.S.); Chlamydia trachomatis; Chlamydophila pneumoniae; Complex; Cytoplasm; Data; Development; Disease; Face; Family; Generations; Gram-Negative Bacteria; Haemophilus influenzae; Helicobacter pylori; Human; IgA-specific serine endopeptidase; Individual; Investigation; Lipase; Mediating; Membrane; Modeling; Molecular; National Institute of Allergy and Infectious Disease; Neisseria meningitidis; Organism; Pathway interactions; Peptide Hydrolases; Play; Positioning Attribute; Process; Prokaryotic Cells; Protein Family; Proteins; Proteobacteria; Pseudomonas aeruginosa; Publishing; Research Personnel; Resistance; Rickettsia rickettsii; Role; Salmonella enterica; Serratia marcescens; Serum; Shigella; Surface; Virulence; Virulence Factors; Work; Yersinia pestis; base; cell envelope; cytotoxicity; esterase; insight; member; mutant; new therapeutic target; novel; pathogen; pathogenic Escherichia coli; periplasm; pertactin; polymerization; public health relevance

DESCRIPTION (provided by applicant): Autotransporters are the most abundant family of secreted proteins in gram-negative bacteria. Many of those that have been characterized are virulence proteins. We have previously shown that autotransporter proteins are secreted at the bacterial pole and that these proteins are targeted to the pole in the bacterial cytoplasm, prior t secretion across the cytoplasmic membrane. Our preliminary data indicate that the cell division protein FtsQ is involved in establishing polar positional information recognized by autotransporters and that the periplasmic domain of FtsQ is sufficient for the generation of this information. We propose exploratory investigations into the role of cell envelope remodeling in the establishment of polar positional information that is recognized in the cytoplasm by autotransporter proteins. Our specific aims are: 1. Characterize mutants of FtsQ defective in establishing polarity of the Shigella spp. autotransporter IcsA. 2. Identify using an unbiased approach, and characterize, proteins in the pathway downstream of FtsQ in autotransporter polarity. 3. Identify using a candidate approach, and characterize, proteins that interact with FtsQ in the autotransporter polarity pathway. The exploratory investigations we propose in this application will generate insights into the mechanisms involved in the establishment of polarity and into the dynamic development and remodeling of the cell envelope in prokaryotes.

描述（由申请人提供）：自转运蛋白是革兰氏阴性细菌中最丰富的分泌蛋白家族。许多已被鉴定的蛋白都是毒力蛋白。我们之前已经证明，自转运蛋白在细菌极处分泌，并且这些蛋白质在穿过细胞质膜分泌之前被靶向细菌细胞质中的极点。我们的初步数据表明，细胞分裂蛋白 FtsQ 参与建立自转运蛋白识别的极性位置信息，并且 FtsQ 的周质结构域足以生成该信息。我们建议对细胞包膜重塑在建立由自转运蛋白在细胞质中识别的极性位置信息中的作用进行探索性研究。我们的具体目标是： 1. 表征在建立志贺氏菌属极性方面存在缺陷的 FtsQ 突变体。自动转运蛋白 IcsA。 2. 使用公正的方法识别并表征自转运蛋白极性中 FtsQ 下游途径中的蛋白质。 3. 使用候选方法识别并表征在自转运蛋白极性途径中与 FtsQ 相互作用的蛋白质。我们在本申请中提出的探索性研究将深入了解原核生物中极性建立所涉及的机制以及细胞包膜的动态发育和重塑。