Post-initiation control of conjugation by plasmid-encoded H-NS and NusG homologs
Post-initiation control of conjugation by plasmid-encoded H-NS and NusG homologs
批准号:
10425461
负责人:
IRINA ARTSIMOVITCH
金额:
$18.78万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-06-09 至 2024-05-31
关键词:
AgricultureAllelesAntibiotic ResistanceAntibioticsBacteriaBacterial AdhesinsBacterial InfectionsBindingCarbapenemsCell WallCenters for Disease Control and Prevention (U.S.)ClinicalColistinCollectionComplexDNADNA-Directed RNA PolymeraseDataDistantElementsElongation FactorEnterobacteriaceaeEscherichia coliEvolutionF FactorFamilyFoodFrequenciesGene Expression RegulationGene SilencingGenesGenomeHistonesHomologous GeneHorizontal Gene TransferHospitalsHumanIn VitroInfectionKlebsiella pneumoniaeLactamaseLearningMaintenanceMediatingModelingOperonPathogenicity IslandPlasmidsPolymyxinsPopulationPrevalenceProcessProductionProphagesProteinsRNARNA chemical synthesisRegulationReportingResistanceResortRho FactorRisk FactorsSamplingShapesSiteSourceStructureTestingToxinTranscription ElongationTranscription InitiationTreatment outcomeVirulenceWorkantibiotic resistant infectionscapsulecarbapenemasecolistin resistancecostcrosslinkexhaustfitnesshelicasehuman pathogenin vivoinsightinterestmembermutantnovelparalogous geneprematurepromoterrecruitresistance generhotermination factortranscription factortranscription factor S-IItranscription termination
中文摘要
项目摘要
许多接合性质粒携带抗病基因,并能在远缘种间转移,
高频率的细菌。已发现携带粘菌素抗性mcr等位基因的质粒
在五大洲的农业,环境和临床样本中,其中一些还
携带超广谱内酰胺酶和碳青霉烯酶基因。这种移动的阻力构成了
质粒是细菌感染治疗的全球性威胁,但对质粒的调控知之甚少。
这一威胁背后的转移。成功的DNA转移需要生产和组装
接合机制的许多组分,其被组织成长的15-30 kb操纵子。
这些操纵子的表达,特别是在异源宿主中的表达,造成显著的适应性成本;
基因组编码的H-NS和其他核相关蛋白(NAPs)沉默表达
外源基因,并且是维持某些质粒所必需的。必须解除沉默,
和干扰H-NS与启动子结合的反沉默剂,
已经描述了启动转录。然而,长异种的表达
操纵子在延伸过程中经常被终止因子Rho沉默,
与H-NS和延伸因子NusG一致,并被操纵子特异性NusG反沉默
旁系亲属许多接合质粒编码H-NS和NusG同源物,我们提出,
包括DNA转移的开关。我们将使用R6 K,一种来自
我们已经知道R6 K编码的H-NX抑制接合。
在目标1中,我们将测试细胞NAP、NusG和Rho对H-NX沉默的影响,确定细胞NAP、NusG和Rho对H-NX沉默的影响。
其靶位点,并研究H-NX募集的机制。在目标2中,我们将测试
ActX是在R6 K转移操纵子内编码的NusG parasites,其激活缀合并
促进RNA合成。我们假设临床上发现的H-NX/ActX对
质粒共同进化以确保其固有质粒的成功传播,
相关的耐药决定因素,通过细菌种群。
英文摘要
PROJECT SUMMARY
Many conjugative plasmids carry antibiotic-resistance genes and can transfer between distant
bacteria at high frequencies. Plasmids carrying colistin-resistance mcr alleles have been found
on five continents in agricultural, environmental, and clinical samples, and several of these also
carry extended-spectrum-lactamase and carbapenemase genes. This mobile resistome poses a
global threat to treatment of bacterial infections, but little is known about the regulation of plasmid
transfer that underlies this threat. Successful DNA transfer requires production and assembly of
many components of the conjugation machinery, which are organized into long 15-30 kb operons.
Expression of these operons, particularly in a heterologous host, imposes significant fitness costs;
genome-encoded H-NS and other nucleoid-associated proteins (NAPs) silence expression of
foreign genes and are required for maintenance of some plasmids. Silencing must be relieved for
conjugation to happen, and counter-silencers that interfere with H-NS binding to promoters and
enable transcription initiation have been described. However, the expression of long xenogeneic
operons is frequently silenced during elongation by the termination factor Rho, which acts in
concert with H-NS and the elongation factor NusG, and counter-silenced by operon-specific NusG
paralogs. Many conjugative plasmids encode H-NS and NusG homologs, which we propose
comprise an off/on switch of DNA transfer. We will use R6K, a model conjugative plasmid from
Escherichia coli, to test this idea; we already know that R6K-encoded H-NX inhibits conjugation.
In Aim 1, we will test the effects of cellular NAPs, NusG and Rho on silencing by H-NX, determine
its target sites, and investigate the mechanism of H-NX recruitment. In Aim 2, we will test whether
ActX, a NusG paralog encoded within the R6K transfer operon, activates conjugation and
promotes processive RNA synthesis. We hypothesize that H-NX/ActX pairs found on clinical
plasmids have co-evolved to assure successful dissemination of their resident plasmids, and
associated resistance determinants, through bacterial populations.
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会议论文
Post-initiation control of conjugation by plasmid-encoded H-NS and NusG homologs
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批准号:10301108
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项目类别:
-
资助金额:$22.21万
-
财政年份:2021
-
负责人:IRINA ARTSIMOVITCH
-
依托单位:
Mechanism of transcript elongation control by RfaH
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Molecular mechanism of antibiotic rifampicin action
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批准号:6911366
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依托单位:
Molecular mechanism of antibiotic rifampicin action
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批准号:7052765
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资助金额:$18.25万
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财政年份:2005
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Mechanism of transcript elongation control by RfaH
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批准号:8231348
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Cellular factors maintaining and reversing silencing of bacterial chromatin
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Mechnanism of transcript elongation control by RfaH
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批准号:7006102
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Mechanism of transcript elongation control by RfaH
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Mechnanism of transcript elongation control by RfaH
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Mechanism of transcript elongation control by RfaH
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Mechnanism of transcript elongation control by RfaH
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Mechanism of transcript elongation control by RfaH
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Mechanism of transcript elongation control by RfaH
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Mechnanism of transcript elongation control by RfaH
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Mechanism of transcript elongation control by RfaH
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Mechanism of transcript elongation control by RfaH
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Mechnanism of transcript elongation control by RfaH
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海外基金