Cell-Cell Signaling, Gene Expression, and Horizontal Gene Transfer in Bacillus

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移动的遗传元件介导，包括 病毒、接合质粒和整合和接合元件（ICE），也称为接合元件 转座子接合元件是众所周知的有助于抗生素基因传播的因子 耐药性、发病机制、共生、代谢等，并在很大程度上负责药物的激增， 耐药和多重耐药细菌病原体。 ICE广泛存在于细菌中，似乎是最普遍的接合元件类型。他们 存在于宿主基因组中。在一定条件下，它们可以切除形成一个圆圈，然后 单链DNA可以转移到合适的受体细胞中。除了调解他们自己的 在转移过程中，ICE可以动员（转移）其他DNA元件，包括质粒，这些元件不能自我转移。 尽管ICE的普遍性和重要性，但我们对ICE的理解存在根本性的缺陷。 这些移动的遗传元素。ICE功能的许多基本机制尚未得到很好的理解，特别是在 革兰氏阳性菌。细菌宿主组分的组分在ICE生物学中起关键作用，但是 这些宿主成分在ICE生命周期中的特性和功能在很大程度上是未知的。ICE通常 与其他移动的遗传因素共存，包括基因。尽管这一事件同时发生， 这些元素对彼此的影响。 移动的遗传元件ICEBs 1是枯草芽孢杆菌中的整合接合元件。ICEBs1 基因表达、切除和交配是在DNA损伤（SOS反应）和 拥挤的条件，前提是相邻单元格不包含元素的副本。的能力 实验性地在群体中几乎所有细胞中诱导ICEBs1，并实现相对高的 共轭使我们能够回答以前棘手的或未研究的问题的根本共轭， HGT 该项目将重点关注：1）新发现的ICEBs 1的性质似乎是广泛保守的， 2)识别和阐明对ICEBs 1生命周期重要的宿主功能，以及3）表征 ICEBs 1和在B的许多菌株的基因组中发现的溶原性噬菌体之间的相互作用。枯草杆菌。基于 同源性和保守的生命周期的ICE，从研究ICEBs1和它的主机，B的见解。 枯草芽孢杆菌，可能是一般相关的许多其他移动的遗传元件和它们的主机。我们的研究结果 应该与细菌之间的基因转移有关，包括那些编码抗生素抗性的基因 生长在许多不同的环境中，包括人类。

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.