Cell-Cell Signaling, Gene Expression, and Horizontal Gene Transfer in Bacillus
Cell-Cell Signaling, Gene Expression, and Horizontal Gene Transfer in Bacillus
批准号:
8628913
负责人:
ALAN D GROSSMAN
金额:
$38.42万
依托单位国家:
美国
项目类别:
财政年份:
1994
资助国家:
美国
项目状态:
已结题
起止时间:
1994-05-01 至 2018-01-31
关键词:
AffectAntibiotic ResistanceAutonomous ReplicationBacillus (bacterium)Bacillus subtilisBacteriaBacterial GenomeBacteriophagesBerylliumBiologicalBiologyCell physiologyCellsCouplingCrowdingDNADNA DamageDrug resistanceElementsEnvironmentEvolutionExcisionExclusionFamilyFrequenciesGene ExpressionGene TransferGenesGeneticGenomeGoalsGram-Positive BacteriaGrowthHomologous GeneHorizontal Gene TransferHumanIndiumInsertion MutationInterleukin ReceptorKnowledgeLife Cycle StagesMediatingMetabolismMicrobeMobile Genetic ElementsMulti-Drug ResistanceMutagenesisPartner in relationshipPathogenesisPhenotypePlasmidsPlayPopulationPrevalencePropertyProteinsReplication OriginRoleSOS ResponseSingle-Stranded DNASiteSymbiosisTestingVirusbasecell killingdriving forcehelicaseinsightintercellular communicationmutantnext generation sequencingoverexpressionpathogenpublic health relevance
中文摘要
水平基因转移(Hgt)是细菌进化的驱动力,使细菌能够获得新的
基因和表型。水平基因转移在很大程度上是由可移动的遗传元件介导的,包括
病毒、接合质粒、整合和接合元件(ICE),也称为接合
转座子。结合元素是众所周知的促进抗生素基因传播的因素
耐药性、致病机制、共生、新陈代谢等,是药物激增的主要原因。
耐药和多重耐药的细菌病原体。
冰在细菌中广泛存在,似乎是最普遍的结合元件类型。他们
驻留在宿主基因组中。在某些条件下,他们可以切除形成一个圆,然后一个
单链DNA可以被转移到合适的受体细胞。除了调解他们自己
在转移过程中,ICES可以动员(转移)其他不能自我转移的DNA元件,包括质粒。
尽管冰的普遍存在和重要性,但我们对冰的理解存在根本缺陷。
这些可移动的遗传元素。ICE功能的许多基本机制还不是很清楚,特别是在
革兰氏阳性细菌。细菌宿主成分在ICE生物学中起着关键作用,但
这些主机组件在内燃机生命周期中的身份和功能在很大程度上是未知的。冰块一般
与包括噬菌体在内的其他移动遗传元素共存。尽管这种情况并存,但人们对此知之甚少。
关于这些元素对彼此的影响。
可移动遗传元件ICEBs1是枯草芽孢杆菌中的一个整合和结合元件。ICEBs1
基因表达、切除和交配是在DNA损伤(SOS反应)和
拥挤条件,前提是相邻单元格不包含该元素的副本。有能力
在实验中几乎在人群中的所有细胞中诱导ICEB1,并实现相对较高的频率
共轭使我们能够回答以前难以解决或未被研究的问题,这些问题是共轭和
HGT。
这个项目将集中在:1)新发现的ICEB1的性质似乎是广泛保守的,
2)确定和阐明对ICEBs1生命周期重要的寄主功能,以及3)特征
ICEBs1与许多枯草杆菌基因组中发现的溶原噬菌体之间的相互作用基座
关于冰的同源性和守恒的生命周期,从研究ICEBs1及其宿主B.
枯草杆菌,通常可能与许多其他可移动的遗传元件及其宿主相关。我们的发现
应该与细菌之间的基因转移有关,包括那些编码抗生素耐药性的基因
在许多不同的环境中生长,包括人类。
英文摘要
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.
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会议论文
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依托单位:
海外基金