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遗传元件介导，包括病毒、接合质粒以及整合和接合元件（ICE），也称为接合转座子。接合元件是众所周知的促进抗生素抗性、发病机制、共生、代谢等基因传播的因素，并且是耐药和多重耐药细菌病原体激增的主要原因。 ICE 在细菌中广泛存在，并且似乎是最普遍的接合元件类型。它们整合在宿主基因组中。在某些条件下，它们可以切除形成一个环，然后将单链 DNA 转移到适当的受体细胞中。除了介导自身转移之外，ICE 还可以动员（转移）其他无法自我转移的 DNA 元件，包括质粒。 尽管 ICE 很普遍且很重要，但我们对这些可移动遗传元件的理解仍然存在根本性缺陷。 ICE 功能的许多基本机制尚不清楚，特别是在革兰氏阳性菌中。细菌宿主成分在 ICE 生物学中发挥着关键作用，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 通常与其他可移动遗传元件（包括噬菌体）共存。尽管存在这种共现现象，但人们对这些元素彼此之间的影响知之甚少。 可移动遗传元件ICEBs1是枯草芽孢杆菌中的整合和接合元件。 ICEBs1 基因表达、切除和交配是在 DNA 损伤（SOS 反应）后和拥挤条件下诱导的，前提是邻近细胞不包含该元件的副本。能够在群体中的几乎所有细胞中通过实验诱导 ICEBs1，并且 实现相对较高的结合频率使我们能够回答以前棘手或未研究的结合和 HGT 的基本问题。 该项目将重点关注：1）新发现的似乎广泛保守的ICEBs1特性，2）识别和阐明对ICEBs1生命周期重要的宿主功能，以及3）表征ICEBs1与基因组中发现的溶原性噬菌体之间的相互作用枯草芽孢杆菌的许多菌株。基于 ICE 的同源性和保守的生命周期，通过研究 ICEBs1 及其宿主枯草芽孢杆菌获得的见解可能与许多其他移动细菌普遍相关。 遗传元件及其宿主。我们的发现应该与在许多不同环境（包括人类）中生长的细菌之间的基因转移相关，包括那些编码抗生素耐药性的基因。