Envelope Biogenesis in Gram-negative Bacteria
革兰氏阴性细菌的包膜生物发生
基本信息
- 批准号:10065723
- 负责人:
- 金额:$ 34.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-07-05 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:ATP phosphohydrolaseATP-Binding Cassette TransportersATPase DomainAddressAffectAnimal ModelAntibiotic ResistanceAntibioticsBacteriaBacterial PhysiologyBacteriophagesBehaviorBindingBiochemicalBiogenesisBioinformaticsBiologicalCarrier ProteinsCell WallCell membraneCell surfaceCellsCommunitiesComplexCoupledCytoplasmDataDevelopmentDiffuseEnvironmentEscherichia coliEukaryotic CellFamilyFundingGeneticGlobular RegionGlycolipidsGoalsGram-Negative BacteriaGrowthHydrophobicityImmune systemIn VitroIndividualInfectionKnowledgeLipid BilayersLipidsLipopolysaccharidesMembraneMembrane ProteinsMolecularMovementNatural ResistanceNucleotidesOrganismPathway interactionsPeptidoglycanPermeabilityPhospholipidsProtein FamilyProteinsResearchResourcesRoleSignal TransductionStructureSurfaceSystemTransmembrane DomainTravelVirulenceWorkantimicrobialantimicrobial drugaqueousbacterial communitybacterial resistancecell communitycell envelopecell motilityenv Gene Productsenvironmental changeglobal healthin vivolipid transportmembrane biogenesisnovelpathogenperiplasmprotein transportweapons
项目摘要
PROJECT SUMMARY
The cell envelope of Gram-negative bacteria is characterized by having two lipid bilayers, the inner membrane
(IM) and the outer membrane (OM). The OM is not a typical biological membrane because while its inner leaflet
contains phospholipids, its outer leaflet is covered with the glycolipid LPS (or lipopolysaccharide). LPS molecules
are densely packed at the cell surface, creating a permeability barrier against small hydrophobic molecules that
otherwise diffuse across phospholipid bilayers. As a result, Gram-negative bacteria are naturally resistant to
many antibiotics. The barrier imposed by LPS is indeed the main reason why very few novel antibiotics effective
against Gram-negative pathogens have been developed in recent years. Therefore, studying OM biogenesis is
not only important to understand bacterial physiology, but also to devise antimicrobial strategies that can
overcome the barrier function of the OM. Our long-term goal is to understand at the molecular level how Gram-
negative bacteria build their cell envelope. Here, we will leverage our expertise in genetic and biochemical
studies of the cell envelope to investigate two highly conserved systems that are essential for OM biogenesis
and growth of the Gram-negative bacterium Escherichia coli. We will investigate how the Lpt system extracts
newly synthesized LPS molecules from the IM so that they can be transported across the cell envelope through
a protein bridge to be assembled at the cell surface. Our studies will focus on how LPS extraction and transport
is powered by the LptB2FGC ATP-binding cassette (ABC) transporter. ABC transporters are ATP-driven
machines that all cells use to translocate substrates across cellular compartments. They are powered by an
ATPase that transduces the energy derived from binding and hydrolyzing ATP to its transmembrane-domain
partners, which translocate the substrate. However, it remains unknown how the actions of the ATPase and
cognate transmembrane domains are coupled so that the transporter can function. The LptB2FGC is functionally
and structurally unusual: it extracts the glycolipid LPS from the IM to place it onto a protein bridge, and its
transmembrane domains LptF/G associate with the transmembrane (TM) helix of another protein, LptC. We
propose to investigate the in vivo role of this unprecedented structural feature, and how the function of the LptB2
ATPase is coupled to the action of the transmembrane domains LptF/G during the LPS transport cycle. To do
so, we will investigate how LptC’s TM helix downregulates ATPase activity, and how uncharacterized functional
domains of LptF/G participate in LPS transport. In addition, we will also study the AsmA-like proteins in E. coli.
This family of proteins remain mostly uncharacterized, but we have discovered they perform a function that is
essential for growth of E. coli. In this funding period, we will advance our understanding of this protein family by
conducting structure-function analyses, identifying their potential partners, and determining their essential
function in OM biogenesis. The proposed research will continue to reveal novel mechanisms that are crucial for
the growth of Gram-negative bacteria and relevant the development of much needed antibiotics.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('Natividad Ruiz', 18)}}的其他基金
Biogenesis of Peptidoglycan in Escherichia coli
大肠杆菌中肽聚糖的生物发生
- 批准号:
8505507 - 财政年份:2012
- 资助金额:
$ 34.75万 - 项目类别:
Biogenesis of Peptidoglycan in Escherichia coli
大肠杆菌中肽聚糖的生物发生
- 批准号:
8908021 - 财政年份:2012
- 资助金额:
$ 34.75万 - 项目类别:
Envelope Biogenesis in Gram-negative Bacteria
革兰氏阴性细菌的包膜生物发生
- 批准号:
10251349 - 财政年份:2012
- 资助金额:
$ 34.75万 - 项目类别:
Envelope Biogenesis in Gram-negative Bacteria
革兰氏阴性细菌的包膜生物发生
- 批准号:
10683987 - 财政年份:2012
- 资助金额:
$ 34.75万 - 项目类别:
Envelope Biogenesis in Gram-negative Bacteria
革兰氏阴性细菌的包膜生物发生
- 批准号:
10462796 - 财政年份:2012
- 资助金额:
$ 34.75万 - 项目类别:
Biogenesis of Peptidoglycan in Escherichia coli
大肠杆菌中肽聚糖的生物发生
- 批准号:
8393936 - 财政年份:2012
- 资助金额:
$ 34.75万 - 项目类别:
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