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

• 批准号: 8798670
• 负责人: ALAN D GROSSMAN
• 金额: $ 38.42万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8798670
• 关键词: Affect; Antibiotic Resistance; Autonomous Replication; Bacillus (bacterium); Bacillus subtilis; Bacteria; Bacterial Genome; Bacteriophages; Beryllium; Biological; Biology; Cell physiology; Cells; Coupling; Crowding; DNA; DNA Damage; Drug resistance; Elements; Environment; Evolution; Excision; Exclusion; Family; Frequencies; Gene Expression; Gene Transfer; Genes; Genetic; Genome; Goals; Gram-Positive Bacteria; Growth; Health; Homologous Gene; Horizontal Gene Transfer; Human; Indium; Insertion Mutation; Interleukin Receptor; Knowledge; Life Cycle Stages; Mediating; Metabolism; Microbe; Mobile Genetic Elements; Multi-Drug Resistance; Mutagenesis; Partner in relationship; Pathogenesis; Phenotype; Plasmids; Play; Population; Prevalence; Property; Proteins; Replication Origin; Role; SOS Response; Single-Stranded DNA; Site; Symbiosis; Testing; Virus; base; cell killing; driving force; helicase; insight; integration site; intercellular communication; mutant; next generation sequencing; overexpression; pathogen

DESCRIPTION (provided by applicant): Horizontal gene transfer (HGT) is a driving force in bacterial evolution, permitting bacteria to acquire new genes and phenotypes. Horizontal gene transfer is largely mediated by mobile genetic elements, including viruses, conjugative plasmids, and integrative and conjugative elements (ICEs), also known as conjugative transposons. Conjugative elements are well known agents contributing to the spread of genes for antibiotic resistances, pathogenesis, symbiosis, metabolism, and more, and are largely responsible for the surge in drug- resistant and multi-drug-resistant bacterial pathogens. ICEs are widespread in bacteria and appear to be the most prevalent type of conjugative element. They reside integrated in a host genome. Under certain conditions, they can excise to form a circle and then a single strand of DNA can be transferred to appropriate recipient cells. In addition to mediating their own transfer, ICEs can mobilize (transfer) other DNA elements, including plasmids, that are not able to self-transfer. Despite the prevalence and importance of ICEs, there are fundamental deficiencies in our understanding of these mobile genetic elements. Many basic mechanisms of ICE function are not well understood, especially in Gram-positive bacteria. Components of the bacterial host components play key roles in ICE biology, but the identities and functions of these host components in the ICE life-cycle are largely unknown. ICEs commonly co-exist with other mobile genetic elements, including phages. Despite this co-occurrence, little is known about effects these elements have on one another. The mobile genetic element ICEBs1 is an integrative and conjugative element in Bacillus subtilis. ICEBs1 gene expression, excision, and mating are induced following DNA damage (the SOS response) and under conditions of crowding, provided that the neighboring cells do not contain a copy of the element. The ability to experimentally induce ICEBs1 in virtually all cells in a population and achieve relatively high frequencies of conjugation allow us to answer previously intractable or unstudied problems fundamental to conjugation and HGT. This project will focus on: 1) newly discovered properties of ICEBs1 that appear to be broadly conserved, 2) identifying and elucidating host functions that are important for ICEBs1 life cycle, and 3) characterizing interactions between ICEBs1 and a lysogenic phage found in the genome of many strains of B. subtilis. Based on homologies and the conserved life cycle of ICEs, insights gained from studying ICEBs1 and its host, B. subtilis, are likely to be generally relevant to many other mobile genetic elements and their hosts. Our findings should be relevant to the transfer of genes, including those encoding antibiotic resistances, between bacteria growing in many different environments, including humans.

描述（由申请人提供）：水平基因转移（HGT）是细菌进化的驱动力，允许细菌获得新的基因和表型。水平基因转移主要由可移动的遗传元件介导，包括病毒、共轭质粒和整合和共轭元件（ICEs），也称为共轭转座子。众所周知，结合元件是促进抗生素耐药性、发病机制、共生、代谢等基因传播的因素，并且在很大程度上是耐药和多重耐药细菌病原体激增的原因。ICEs在细菌中广泛存在，似乎是最普遍的共轭元件类型。它们整合在宿主基因组中。在一定条件下，它们可以切除形成一个圆圈，然后将单链DNA转移到合适的受体细胞中。除了介导自身的转移外，ice还可以调动（转移）其他无法自我转移的DNA元件，包括质粒。尽管ice的普遍性和重要性，但我们对这些可移动遗传因素的理解存在根本缺陷。许多ICE功能的基本机制尚不清楚，特别是革兰氏阳性菌。细菌宿主成分在ICE生物学中起着关键作用，但这些宿主成分在ICE生命周期中的身份和功能在很大程度上是未知的。ice通常与其他可移动的遗传元素共存，包括噬菌体。尽管有这种共存现象，但人们对这些元素彼此之间的影响知之甚少。移动遗传因子ICEBs1是枯草芽孢杆菌的整合偶联基因。ICEBs1基因的表达、切除和交配是在DNA损伤（SOS反应）和拥挤条件下诱导的，前提是邻近细胞不含有该元件的拷贝。能够在一个群体中几乎所有细胞中实验诱导ICEBs1