Cell-cell signaling, gene expression, and horizontal gene transfer in Bacillus

芽孢杆菌中的细胞间信号传导、基因表达和水平基因转移

基本信息

批准号：
7900255
负责人：
ALAN D GROSSMAN
金额：
$ 21.55万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7900255
关键词：
Affect Antibiotic Resistance Bacillus (bacterium)Bacillus anthracis Bacillus subtilis Bacteria Bacteriophages Biological Cell Communication Cell physiology Cells Cellular biology Chromosomes Cleaved cell DNA DNA Damage Development Elements Enterococcus faecalis Evolution Excision Figs - dietary Gene Expression Genes Genome Goals Gram-Positive Bacteria Grant Growth Homologous Gene Horizontal Gene Transfer Hormones Hour Indium Individual Location Maintenance Measures Mediating Microbe Mobile Genetic Elements Modeling Monitor Neurotransmitters Organism Partner in relationship Pathogenesis Peptide Hydrolases Peptides Pheromone Plasmids Play Positioning Attribute Process Proteins Proteolysis Regulation Repression Reproduction spores Role SOS Response Signal Induction Signal Transduction Signaling Molecule Site Specificity Staphylococcus aureus Streptococcus pneumoniae Symbiosis Testing computerized data processing excisionase human disease insight intercellular communication microbial public health relevance response segregation

项目摘要

DESCRIPTION (provided by applicant): Cell-cell signaling controls many processes in the biological world, including development, pathogenesis, growth, transformation, and mating. Signaling processes are often mediated by diffusible factors (e.g., hormones, pheromones, neurotransmitters) that are produced by some cells and sensed by others. In addition to diffusible signaling molecules, one of the most intimate forms of cell-cell communication involves conjugation and horizontal gene transfer. Mating responses in microbes are often mediated by peptide pheromones. The long term goal of this project is to understand how cells modulate gene expression and horizontal gene transfer in response to environmental conditions, with emphasis on cell-cell signaling and the regulatory mechanisms controlling a mobile genetic element in the bacterium Bacillus subtilis. Mobile genetic elements include phages, conjugative plasmids, and conjugative transposons, also known as integrative and conjugative elements (ICEs). Mobile genetic elements play significant roles in evolution, genome plasticity, symbiosis, pathogenesis, and the spread of antibiotic resistance. Despite their importance, relatively little is known about the mechanisms regulating ICEs in Gram-positive organisms. The mobile genetic element ICEBs1 is an integrative and conjugative element in Bacillus subtilis. It resides in the B. subtilis chromosome and is stably propagated with the host chromosome. ICEBs1 gene expression, excision, replication, and mating are regulated by a cell-cell signaling response and induced upon DNA damage (the SOS response). This project will focus on mechanisms of ICEBs1 regulation and function that appear to be broadly conserved and that are not well-understood in Gram-positives. The project includes: elucidation of the mechanisms of induction mediated by a conserved anti-repressor and repressor and their regulation by DNA damage and cell-cell signaling; determination of the mechanisms and functions of replication of ICEBs1 in donor cells after excision and how replication contributes to horizontal gene transfer and stability of ICEBs1; determination of roles of conserved cell-cell signaling modules in the control of horizontal gene transfer in other mobile elements. Our studies on cell-cell signaling, gene expression, and horizontal gene transfer in B. subtilis, a relatively simple, experimentally accessible microbe, should provide insights into general mechanisms used in many organisms. PUBLIC HEALTH RELEVANCE: Mobile genetic elements and horizontal gene transfer in microbes contribute significantly to pathogenesis and the spread of antibiotic resistances. This project investigates a common type of mobile genetic element that is found in many different organisms, especially Gram-positive bacteria exemplified by Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis and Bacillus anthracis, that cause serious human disease.

描述（由申请人提供）：细胞间信号传导控制生物界的许多过程，包括发育、发病机制、生长、转化和交配。信号传导过程通常由一些细胞产生并被其他细胞感知的扩散因子（例如激素、信息素、神经递质）介导。除了可扩散的信号分子之外，细胞间通讯最密切的形式之一涉及接合和水平基因转移。微生物的交配反应通常由肽信息素介导。该项目的长期目标是了解细胞如何调节基因表达和水平基因转移以响应环境条件，重点是细胞间信号传导和控制枯草芽孢杆菌中移动遗传元件的调节机制。移动遗传元件包括噬菌体、接合质粒和接合转座子，也称为整合和接合元件（ICE）。移动遗传元件在进化、基因组可塑性、共生、发病机制和抗生素耐药性的传播中发挥着重要作用。尽管它们很重要，但人们对革兰氏阳性生物体中 ICE 的调节机制知之甚少。可移动遗传元件ICEBs1是枯草芽孢杆菌中的整合和接合元件。它驻留在枯草芽孢杆菌染色体中，并与宿主染色体一起稳定繁殖。 ICEBs1 基因表达、切除、复制和交配受细胞间信号传导反应调节，并在 DNA 损伤（SOS 反应）时诱导。该项目将重点关注 ICEBs1 的调节和功能机制，这些机制似乎广泛保守，但在革兰氏阳性菌中尚未得到充分理解。该项目包括：阐明保守的抗阻遏物和阻遏物介导的诱导机制及其通过 DNA 损伤和细胞信号转导的调节；确定切除后供体细胞中ICEBs1复制的机制和功能，以及复制如何促进ICEBs1的水平基因转移和稳定性；确定保守的细胞间信号传导模块在控制其他移动元件中的水平基因转移中的作用。我们对枯草芽孢杆菌（一种相对简单、可通过实验获得的微生物）的细胞间信号传导、基因表达和水平基因转移的研究，应该可以为许多生物体中使用的一般机制提供见解。公共卫生相关性：微生物中的移动遗传元件和水平基因转移对抗生素耐药性的发病机制和传播有重大影响。该项目研究了在许多不同生物体中发现的一种常见类型的移动遗传元件，特别是革兰氏阳性细菌，例如金黄色葡萄球菌、肺炎链球菌、粪肠球菌和炭疽杆菌，它们会导致严重的人类疾病。