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

描述（由申请人提供）：细胞-细胞信号传导控制生物世界中的许多过程，包括发育、发病、生长、转化和交配。信号传导过程通常由可扩散因子介导（例如，激素，信息素，神经递质），由一些细胞产生，并由其他细胞感知。除了可扩散的信号分子外，细胞间通讯最密切的形式之一还包括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-细胞信号传导和控制细菌枯草芽孢杆菌中移动的遗传元件的调节机制。移动的遗传元件包括整合元件、接合质粒和接合转座子，也称为整合和接合元件（ICE）。移动的遗传元件在进化、基因组可塑性、共生、致病和抗生素耐药性的传播中起着重要作用。尽管它们的重要性，相对较少的是知道的机制，在革兰氏阳性菌调节ICE。移动的遗传元件ICEBs 1是枯草芽孢杆菌中的整合接合元件。它位于B区。枯草芽孢杆菌染色体，并与宿主染色体稳定繁殖。ICEBs 1基因表达、切除、复制和交配受细胞-细胞信号传导反应调节，并在DNA损伤后诱导（SOS反应）。该项目将侧重于ICEBs 1的调节和功能的机制，这些机制似乎是广泛保守的，并且在革兰氏阳性菌中还没有得到很好的理解。项目内容包括：阐明由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-细胞信号传导的调节;确定切除后ICEBs 1在供体细胞中复制的机制和功能以及复制如何有助于ICEBs 1的水平基因转移和稳定性;确定保守的细胞-细胞信号传导模块在控制其他移动的元件中的水平基因转移中的作用。我们对B细胞间信号传导、基因表达和水平基因转移的研究。枯草芽孢杆菌是一种相对简单的、实验上可获得的微生物，它应该能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：微生物中的移动的遗传元件和水平基因转移对抗生素耐药性的发病和传播有重要作用。本项目研究了一种常见的移动的遗传因子，这种遗传因子存在于许多不同的生物体中，特别是革兰氏阳性菌，如金黄色葡萄球菌、肺炎链球菌、粪肠球菌和炭疽杆菌，这些细菌会导致严重的人类疾病。

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.