Role of a cell wall assembly factor in enterococcal antimicrobial resistance
Role of a cell wall assembly factor in enterococcal antimicrobial resistance
批准号:
9225316
负责人:
CHRISTOPHER J KRISTICH
金额:
$23.1万
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-07-10 至 2019-06-30
关键词:
AddressAlpha CellAntibiotic ResistanceAntibioticsAntimicrobial ResistanceBacteriaBile fluidBindingBiochemicalBiologicalBiological AdaptationCell WallCell divisionCenters for Disease Control and Prevention (U.S.)Cephalosporin ResistanceCephalosporinsCholatesComplexCytoplasmDataDetergentsDevelopmentEmployee StrikesEnterococcusEnterococcus faecalisEscherichia coliFamilyFoundationsFutureGeneticGenetic EpistasisGram-Positive BacteriaHomeostasisHomologous GeneInfectionIntegral Membrane ProteinInterventionKnowledgeMediatingMembrane ProteinsModelingMolecularMonitorMulti-Drug ResistanceNosocomial InfectionsPeptidoglycanPhenotypePhosphotransferasesProcessProductionReportingResearchResistanceRoleSignal TransductionStimulusStressSystemTestingTherapeuticToxinUnited StatesVirulenceWorkdesignextracellularin vivoinnovationinsightmutantnew therapeutic targetnovelnovel therapeutic interventionnovel therapeuticspathogenic bacteriaprotein complexprotein protein interactionresponseretinal rodssensory input
中文摘要
项目摘要
几乎所有的革兰氏阳性细菌都合成一种跨膜的Ser/Thr激酶,其含有3-5
细胞外PASTA结构域(“PASTA激酶”),控制关键过程,包括抗生素
抗性、毒素产生、毒力或细胞分裂;在某些细菌中,这种激酶对于
生存能力。因此,这些激酶代表了新疗法的有吸引力的靶标。然而,一个基本的
了解该家族中激酶的功能机制,以感知环境
缺乏体内刺激并处理信息以协调适应性生物反应。
这些信息对于开发新的治疗方法至关重要。研究
这里提出的旨在帮助解决这一差距,阐明基本方面的功能,
该家族中的代表性激酶,即粪肠球菌中的IreK激酶,我们已经证明,
E的固有电阻所需。粪便中存在的细胞壁活性抗生素和洗涤剂
胆汁,如胆酸盐。这项研究旨在阐明IreK功能的新见解
激酶与其他细胞壁组装因子的物理和功能关系。
粪便特别是,我们将定义一种蛋白质复合物的组成,这种蛋白质复合物被认为参与了
细胞壁组装,评估其在内在抗菌素耐药性中的作用,并检查其相互作用,
了解IreK如何履行其职责。这项工作有
建立细菌中PASTA激酶跨膜信号转导新模型的潜力,
为抗菌素耐药性、细胞壁完整性的协调、毒力和
革兰氏阳性菌的其他过程。
英文摘要
PROJECT SUMMARY
Nearly all Gram-positive bacteria synthesize a transmembrane, Ser/Thr kinase containing 3-5
extracellular PASTA-domains (‘PASTA kinase’) that controls critical processes including antibiotic
resistance, toxin production, virulence, or cell division; in some bacteria this kinase is essential for
viability. As such, these kinases represent attractive targets for new therapeutics. However, a basic
understanding of the mechanisms by which kinases in this family function to perceive environmental
stimuli in vivo and process that information to coordinate adaptive biological responses is lacking.
Such information is critical to inform development of new therapeutic approaches. The research
proposed here seeks to help address this gap by elucidating fundamental aspects of function for a
representative kinase in this family, the IreK kinase in Enterococcus faecalis, which we have shown is
required for intrinsic resistance of E. faecalis to cell-wall-active antibiotics and to detergents present in
bile, such as cholate. This research is designed to elucidate new insights into the function of the IreK
kinase by exploring its physical and functional relationships with other cell wall assembly factors in E.
faecalis. In particular, we will define the composition of a protein complex thought to be involved in
cell wall assembly, assess its role in intrinsic antimicrobial resistance, and examine its interactions both
physical and functional with IreK to understand how IreK carries out its duties. This work has the
potential to establish a new model for transmembrane signaling by PASTA kinases in bacteria and
provide new insights into antimicrobial resistance, coordination of cell wall integrity, virulence and
other processes in Gram-positive bacteria.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Host factors required for vancomycin resistance in enterococci
-
批准号:10215113
-
项目类别:
-
资助金额:$19.5万
-
财政年份:2021
-
负责人:CHRISTOPHER J KRISTICH
-
依托单位:
Host factors required for vancomycin resistance in enterococci
-
批准号:10339472
-
项目类别:
-
资助金额:$23.4万
-
财政年份:2021
-
负责人:CHRISTOPHER J KRISTICH
-
依托单位:
Role and regulation of peptidoglycan synthases in enterococcal antimicrobial resistance
-
批准号:10558661
-
项目类别:
-
资助金额:$47.66万
-
财政年份:2020
-
负责人:CHRISTOPHER J KRISTICH
-
依托单位:
Role and regulation of peptidoglycan synthases in enterococcal antimicrobial resistance
-
批准号:10348714
-
项目类别:
-
资助金额:$47.66万
-
财政年份:2020
-
负责人:CHRISTOPHER J KRISTICH
-
依托单位:
Conformation and functional dynamics of a bacterial PASTA kinase
-
批准号:10526288
-
项目类别:
-
资助金额:$33.88万
-
财政年份:2020
-
负责人:CHRISTOPHER J KRISTICH
-
依托单位:
Conformation and functional dynamics of a bacterial PASTA kinase
-
批准号:10302266
-
项目类别:
-
资助金额:$33.88万
-
财政年份:2020
-
负责人:CHRISTOPHER J KRISTICH
-
依托单位:
Analysis of PASTA kinase function in Enterococcus faecalis
-
批准号:9451474
-
项目类别:
-
资助金额:$24.24万
-
财政年份:2018
-
负责人:CHRISTOPHER J KRISTICH
-
依托单位:
Intrinsic cephalosporin resistance in enterococci
-
批准号:9419533
-
项目类别:
-
资助金额:$38.5万
-
财政年份:2018
-
负责人:CHRISTOPHER J KRISTICH
-
依托单位:
Genes of unknown function impacting antimicrobial resistance in enterococci
-
批准号:9370219
-
项目类别:
-
资助金额:$23.1万
-
财政年份:2017
-
负责人:CHRISTOPHER J KRISTICH
-
依托单位:
Bacteriophage to prevent infection by antibiotic-resistant enterococci
-
批准号:9018963
-
项目类别:
-
资助金额:$23.01万
-
财政年份:2015
-
负责人:CHRISTOPHER J KRISTICH
-
依托单位:
Impact of nucleotide metabolism on enterococcal antibiotic resistance
-
批准号:8777943
-
项目类别:
-
资助金额:$19.13万
-
财政年份:2013
-
负责人:CHRISTOPHER J KRISTICH
-
依托单位:
Impact of nucleotide metabolism on enterococcal antibiotic resistance
-
批准号:8617698
-
项目类别:
-
资助金额:$22.95万
-
财政年份:2013
-
负责人:CHRISTOPHER J KRISTICH
-
依托单位:
Enterococcus niche formation in the GI tract
-
批准号:8494555
-
项目类别:
-
资助金额:$17.98万
-
财政年份:2012
-
负责人:CHRISTOPHER J KRISTICH
-
依托单位:
Enterococcus niche formation in the GI tract
-
批准号:8374087
-
项目类别:
-
资助金额:$22.95万
-
财政年份:2012
-
负责人:CHRISTOPHER J KRISTICH
-
依托单位:
Intrinsic Resistance to antimicrobials in Enterococcus faecalis
-
批准号:8389646
-
项目类别:
-
资助金额:$35.36万
-
财政年份:2009
-
负责人:CHRISTOPHER J KRISTICH
-
依托单位:
Genetic approaches to protein-protein interactions mediating antibiotic resistanc
-
批准号:7847398
-
项目类别:
-
资助金额:$228.0万
-
财政年份:2009
-
负责人:CHRISTOPHER J KRISTICH
-
依托单位:
Intrinsic Resistance to antimicrobials in Enterococcus faecalis
-
批准号:7993563
-
项目类别:
-
资助金额:$37.62万
-
财政年份:2009
-
负责人:CHRISTOPHER J KRISTICH
-
依托单位:
Intrinsic Resistance to antimicrobials in Enterococcus faecalis
-
批准号:8197072
-
项目类别:
-
资助金额:$37.62万
-
财政年份:2009
-
负责人:CHRISTOPHER J KRISTICH
-
依托单位:
Intrinsic Resistance to antimicrobials in Enterococcus faecalis
-
批准号:8586291
-
项目类别:
-
资助金额:$37.62万
-
财政年份:2009
-
负责人:CHRISTOPHER J KRISTICH
-
依托单位:
Intrinsic Resistance to antimicrobials in Enterococcus faecalis
-
批准号:7779367
-
项目类别:
-
资助金额:$38.0万
-
财政年份:2009
-
负责人:CHRISTOPHER J KRISTICH
-
依托单位:
海外基金