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
项目总结
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.
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依托单位:
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财政年份:2012
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依托单位:
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依托单位:
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资助金额:$37.62万
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财政年份:2009
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依托单位:
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项目类别:
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财政年份:2009
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资助金额:$38.0万
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依托单位:
海外基金