Rethinking the barrier: How a Gram-negative bacterium alters its surface to become multidrug resistant
重新思考屏障:革兰氏阴性细菌如何改变其表面以产生多重耐药性
基本信息
- 批准号:9102680
- 负责人:
- 金额:$ 22.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-06-15 至 2017-05-31
- 项目状态:已结题
- 来源:
- 关键词:Acinetobacter baumanniiAnabolismAntibiotic ResistanceAntibioticsArchitectureBacteriaBasic ScienceBindingBiochemicalBloodCell Membrane PermeabilityCell SurvivalCellsCessation of lifeCiprofloxacinClinicalColistinComplexCytolysisDevelopmentDrug resistanceExposure toExtravasationExtreme drug resistant tuberculosisFutureGenesGeneticGlycerophospholipidsGram-Negative BacteriaHealthHealthcareHigh-Throughput Nucleotide SequencingInfectionKnowledgeLaboratoriesLeadLifeLipid ALipopolysaccharide Biosynthesis PathwayLipopolysaccharidesLungMedicalMembraneMethodsMolecularMolecular TargetMulti-Drug ResistanceMutagenesisMutationNosocomial InfectionsOutcomePatientsPermeabilityPhenotypePhospholipidsPolymyxinsPropertyProteomicsProtocols documentationPublic HealthResistanceResistance developmentResortStructureSurfaceSurgical woundUrinary tract infectionVaccinesWorkantimicrobialbaseclinically relevantcolistin resistanceeffective therapygenome sequencingimprovedinorganic phosphatelipooligosaccharideloss of function mutationmonolayernovelnovel therapeuticspathogenpreventresistance generesistance mechanismtigecyclinetranscriptome sequencing
项目摘要
DESCRIPTION (provided by applicant): Bacterial pathogens exploit various molecular mechanisms to survive unpredictable and adverse environmental conditions. Gram-negative bacteria often alter their environmentally exposed outer membrane, an asymmetric bilayer consisting of inner leaflet glycerophospholipids and essential outer leaflet lipooligosaccharide (LPS) or lipopolysaccharide (LOS). Acinetobacter baumannii is a Gram-negative nosocomial pathogen that thrives in healthcare settings because of its ability to develop resistance to antibiotics. Multidrug resistant A. baumannii have become widespread over the past decade and last-line antibiotics such as colistin, which target the essential LOS in the outer membrane, have been increasingly prescribed to treat multidrug resistant infections. While colistin resistance was
once rare, this is no longer the case, especially regarding A. baumannii. Uniquely, A. baumannii can completely shutdown LOS biosynthesis to develop resistance to colistin and many other commonly prescribed antibiotics. This finding is surprising since LPS/LOS are typically essential for Gram-negative bacterial viability. Mechanisms that contribute to LOS deficiency and the resulting multidrug resistance phenotype are not understood. The overall objective of this proposal is to characterize and understand a novel multidrug resistance mechanism. The Specific Aims of this proposal are (i) to understand the genetic requirements for complete loss of LOS and (ii) to characterize the altered outer membrane permeability barrier in LOS deficient A. baumannii. Completion of this work will contribute a critical body of knowledge to the essentiality of LPS/LOS in Gram-negative bacteria and provide understanding of the molecular mechanisms required for a novel multidrug resistance mechanism. The basic science framework from this proposal could also potentially lead to development of novel therapeutics and improved vaccines.
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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Michael Stephen Trent其他文献
Michael Stephen Trent的其他文献
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{{ truncateString('Michael Stephen Trent', 18)}}的其他基金
The role of cardiolipin in the biogenesis of the Gram-negative bacterial cell envelope
心磷脂在革兰氏阴性细菌细胞包膜生物发生中的作用
- 批准号:
10731444 - 财政年份:2023
- 资助金额:
$ 22.5万 - 项目类别:
Synthesis and transport of outer membrane components across the Gram-negative cell envelope
外膜成分的合成和跨革兰氏阴性细胞包膜的运输
- 批准号:
10680968 - 财政年份:2023
- 资助金额:
$ 22.5万 - 项目类别:
The Cell Envelope of the Multi-Drug Resistant Pathogen Acinetobacter baumannii
多重耐药病原体鲍曼不动杆菌的细胞包膜
- 批准号:
10113527 - 财政年份:2020
- 资助金额:
$ 22.5万 - 项目类别:
The Cell Envelope of the Multi-Drug Resistant Pathogen Acinetobacter baumannii
多重耐药病原体鲍曼不动杆菌的细胞包膜
- 批准号:
10542396 - 财政年份:2020
- 资助金额:
$ 22.5万 - 项目类别:
The Cell Envelope of the Multi-Drug Resistant Pathogen Acinetobacter baumannii
多重耐药病原体鲍曼不动杆菌的细胞包膜
- 批准号:
10328269 - 财政年份:2020
- 资助金额:
$ 22.5万 - 项目类别:
Molecular mechanisms required for the maintenance of the gram-negative outer membrane
维持革兰氏阴性外膜所需的分子机制
- 批准号:
10159193 - 财政年份:2018
- 资助金额:
$ 22.5万 - 项目类别:
Molecular mechanisms required for the maintenance of the gram-negative outer membrane
维持革兰氏阴性外膜所需的分子机制
- 批准号:
10403653 - 财政年份:2018
- 资助金额:
$ 22.5万 - 项目类别:
Molecular mechanisms required for the maintenance of the gram-negative outer membrane
维持革兰氏阴性外膜所需的分子机制
- 批准号:
9917747 - 财政年份:2018
- 资助金额:
$ 22.5万 - 项目类别:
Development of a novel vaccine platform: Surface Antigen/Adjuvant Vaccine Engineering (SAAVE)
新型疫苗平台的开发:表面抗原/佐剂疫苗工程(SAAVE)
- 批准号:
9899172 - 财政年份:2017
- 资助金额:
$ 22.5万 - 项目类别:
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