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

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），也称为接合转座子。缀合元件是有助于抗生素抗性、发病机理、共生、代谢等基因传播的众所周知的因子，并且主要负责抗药性和多重抗药性细菌病原体的激增。 ICE广泛存在于细菌中，似乎是最普遍的接合元件类型。它们整合在宿主基因组中。在一定条件下，它们可以切割形成一个环，然后可以将单链DNA转移到合适的受体细胞中。除了介导自身的转移外，ICE还可以动员（转移）其他不能自我转移的DNA元件，包括质粒。 尽管ICE的普遍性和重要性，我们对这些移动的遗传因素的理解存在根本性的缺陷。ICE功能的许多基本机制尚未完全了解，特别是在革兰氏阳性菌中。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通常与其他移动的遗传元素共存，包括生物素。尽管这种共同发生，很少有人知道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基因的表达，切除和交配诱导后DNA损伤（SOS反应）和拥挤的条件下，提供了相邻的细胞不包含一个副本的元素。在群体中的几乎所有细胞中实验诱导ICEBs 1的能力， 实现相对高的共轭频率使我们能够回答以前难以解决的或未研究的共轭和HGT的基本问题。 该项目将侧重于：1）新发现的ICEBs 1的特性似乎是广泛保守的，2）鉴定和阐明对ICEBs 1生命周期重要的宿主功能，和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，很可能是一般相关的许多其他移动的 遗传因子及其宿主我们的发现应该与基因的转移有关，包括那些编码抗生素耐药性的基因，在许多不同环境中生长的细菌之间，包括人类。

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.