Host-mediated zinc sequestration during Acinetobacter baumannii infection
鲍曼不动杆菌感染期间宿主介导的锌螯合
基本信息
- 批准号:8504420
- 负责人:
- 金额:$ 43.14万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-01-15 至 2017-12-31
- 项目状态:已结题
- 来源:
- 关键词:AcinetobacterAcinetobacter baumanniiAdvanced Glycosylation End ProductsAffectAntibioticsAntimicrobial EffectAntimicrobial ResistanceAreaBacteremiaBacteriaBacterial Drug ResistanceBacterial InfectionsBindingBiologyCommunicable DiseasesCoupledDataDevelopmentDiseaseEndocarditisEnsureEventExhibitsFoundationsGrowthHost DefenseImmuneImmune responseImmunityIn VitroInfectionInfectious AgentInflammationInflammatoryIntensive Care UnitsIronLeadLeukocyte L1 Antigen ComplexLigandsLungManganeseMeasuresMediatingMeningitisMetalsMolecularMusMutationNutrientNutritionalOrganismOutcomePathogenesisPeptidesPhysiologyPneumoniaProcessProductionProteinsPublic HealthReceptor ActivationRecruitment ActivityRegulonRelative (related person)ResistanceRespiratory SystemRespiratory tract structureRoleSentinelSeriesSignal PathwaySignal TransductionSiteSystemTechnologyTestingTherapeuticTherapeutic InterventionTransition ElementsUrinary tract infectionVertebratesWorkWound InfectionZincantimicrobialbasechelationclinically significantcombatdefined contributiondesigninsightmicrobialmutantneutrophilnew therapeutic targetnovelpathogenpreventpublic health relevancereceptorreceptor bindingresearch studyscaffoldtherapeutic developmenttherapy designthree dimensional structureuptake
项目摘要
DESCRIPTION (provided by applicant): Acinetobacter baumannii is an important nosocomial pathogen that causes a range of diseases, including respiratory and urinary tract infections, meningitis, endocarditis, wound infections, and bacteremia. In fact, A. baumannii is now responsible for up to 20% of all intensive care unit infections in some regions of the world with pneumonia being the most common presentation. The clinical significance of A. baumannii has been propelled by this organism's rapid acquisition of resistance to virtually all antibiotics. The
identification of novel targets for therapeutic intervention is critical to our ability to protect he public health from this emerging infectious threat. One promising potential area of therapeutic development involves targeting bacterial access to nutrient metal. This strategy is based on the fact that all bacterial pathogens require nutrient metal in order to colonize their hosts. Despite the fact that a variety of metals are required by bacterial pathogens during growth within vertebrates, iron sequestration is considered to be the primary nutrient that is actively sequestered by the host during the innate immune response to infection. In the present application, we provide evidence that the innate immune factor calprotectin defends against Acinetobacter pneumonia by chelating nutrient zinc (Zn). Using calprotectin as a probe, we have identified a transport system in A. baumannii that competes with calprotectin for Zn and is transcriptionally controlled by a Zn-dependent regulator. Calprotectin is abundant at sites of inflammation and is a known pro- inflammatory molecule that is a ligand for the receptor for advanced glycation end products (RAGE). Despite its clear involvement, the contributions of calprotectin-mediated metal sequestration and RAGE binding to defense against infection have not been thoroughly evaluated. Based on preliminary data described in this application, we hypothesize that calprotectin-mediated Zn sequestration and RAGE binding are critical factors during the host-pathogen interaction. To test this central hypothesis, we propose a series of experiments aimed at understanding the mechanism and pathophysiological consequence of calprotectin-mediated Zn sequestration and RAGE binding during A. baumannii pneumonia. In these studies, we will (i) identify the structural features of calprotectin that enable it to chelae transition metals such as Zn and to bind RAGE, (ii) elucidate the impact of calprotectin and RAGE on A. baumannii pathogenesis, and (iii) determine the impact of CP-mediated Zn chelation on the physiology of A. baumannii. These results will provide fundamental insight into how A. baumannii acquires nutrients in the vertebrate host, and lay the foundation for the creation of peptide therapeutics based on a calprotectin scaffold that inhibit microbial growth through nutrient metal chelation.
描述(由申请人提供):鲍曼不动杆菌是一种重要的院内病原体,可引起一系列疾病,包括呼吸道和尿路感染、脑膜炎、心内膜炎、伤口感染和菌血症。事实上,鲍曼不动杆菌目前在世界某些地区的所有重症监护病房感染中占20%,肺炎是最常见的表现。鲍曼不动杆菌对几乎所有抗生素的快速耐药性推动了它的临床意义。的
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
WALTER J. CHAZIN其他文献
WALTER J. CHAZIN的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('WALTER J. CHAZIN', 18)}}的其他基金
The XPA scaffold protein in Nucleotide Excision Repair
核苷酸切除修复中的 XPA 支架蛋白
- 批准号:
10733350 - 财政年份:2018
- 资助金额:
$ 43.14万 - 项目类别:
The XPA scaffold protein in Nucleotide Excision Repair
核苷酸切除修复中的 XPA 支架蛋白
- 批准号:
10334466 - 财政年份:2018
- 资助金额:
$ 43.14万 - 项目类别:
Structural Biology of Multi-Domain Proteins and Multi-Protein Machinery in DNA Replication and Repair
DNA 复制和修复中多域蛋白和多蛋白机制的结构生物学
- 批准号:
10393403 - 财政年份:2016
- 资助金额:
$ 43.14万 - 项目类别:
Integrative Structural Biology in DNA Replication and Damage Response
DNA 复制和损伤反应中的综合结构生物学
- 批准号:
10796477 - 财政年份:2016
- 资助金额:
$ 43.14万 - 项目类别:
Structural Biology of Multi-Domain Proteins and Multi-Protein Machinery in DNA Replication and Repair
DNA 复制和修复中多域蛋白和多蛋白机制的结构生物学
- 批准号:
10382072 - 财政年份:2016
- 资助金额:
$ 43.14万 - 项目类别:
Integrative Structural Biology in DNA Replication and Damage Response
DNA 复制和损伤反应中的综合结构生物学
- 批准号:
10330665 - 财政年份:2016
- 资助金额:
$ 43.14万 - 项目类别:
Integrative Structural Biology in DNA Replication and Damage Response
DNA 复制和损伤反应中的综合结构生物学
- 批准号:
10544307 - 财政年份:2016
- 资助金额:
$ 43.14万 - 项目类别:
Integrative Structural Biology in DNA Replication and Damage Response
DNA 复制和损伤反应中的综合结构生物学
- 批准号:
10809376 - 财政年份:2016
- 资助金额:
$ 43.14万 - 项目类别:
Host-mediated zinc sequestration during Acinetobacter baumannii infection
鲍曼不动杆菌感染期间宿主介导的锌螯合
- 批准号:
10680779 - 财政年份:2013
- 资助金额:
$ 43.14万 - 项目类别:
Host-mediated zinc sequestration during Acinetobacter baumannii infection
鲍曼不动杆菌感染期间宿主介导的锌螯合
- 批准号:
10331783 - 财政年份:2013
- 资助金额:
$ 43.14万 - 项目类别:
相似海外基金
Isolation and characterisation of monoclonal antibodies for the treatment or prevention of antibiotic resistant Acinetobacter baumannii infections
用于治疗或预防抗生素耐药鲍曼不动杆菌感染的单克隆抗体的分离和表征
- 批准号:
MR/Y008693/1 - 财政年份:2024
- 资助金额:
$ 43.14万 - 项目类别:
Research Grant
Generative machine learning for narrow spectrum antibiotic discovery against Acinetobacter baumannii
生成机器学习用于发现针对鲍曼不动杆菌的窄谱抗生素
- 批准号:
477936 - 财政年份:2023
- 资助金额:
$ 43.14万 - 项目类别:
Operating Grants
Conserved structural dynamics of outer-membrane channels in Acinetobacter baumannii as potential drug targets
鲍曼不动杆菌外膜通道的保守结构动力学作为潜在的药物靶点
- 批准号:
494854 - 财政年份:2023
- 资助金额:
$ 43.14万 - 项目类别:
Operating Grants
Defining key players at the host-pathogen interface during Acinetobacter baumannii infection
定义鲍曼不动杆菌感染期间宿主-病原体界面的关键参与者
- 批准号:
488684 - 财政年份:2023
- 资助金额:
$ 43.14万 - 项目类别:
Operating Grants
Study of clinically over-expressed and chimeric RND multidrug efflux pumps from Acinetobacter baumannii and Pseudomonas aeruginosa
鲍曼不动杆菌和铜绿假单胞菌临床过表达和嵌合 RND 多药外排泵的研究
- 批准号:
23K14346 - 财政年份:2023
- 资助金额:
$ 43.14万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Biomimetic Macrophage Membrane-Coated Nanosponges: A Novel Therapeutic for Multidrug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii Hospital-Associated Pneumonia
仿生巨噬细胞膜包被的纳米海绵:一种治疗多重耐药铜绿假单胞菌和鲍曼不动杆菌医院相关肺炎的新疗法
- 批准号:
10674406 - 财政年份:2023
- 资助金额:
$ 43.14万 - 项目类别:
Using strain history to improve prediction of the evolution of antimicrobial resistance in Acinetobacter baumannii
利用菌株历史改进对鲍曼不动杆菌抗菌药物耐药性演变的预测
- 批准号:
10677362 - 财政年份:2023
- 资助金额:
$ 43.14万 - 项目类别:
Inhibitors of adaptive efflux mediated resistance in Acinetobacter baumannii
鲍曼不动杆菌适应性外排介导的耐药性抑制剂
- 批准号:
10625029 - 财政年份:2023
- 资助金额:
$ 43.14万 - 项目类别:
Identifying niche specific adaptations in Acinetobacter baumannii
鉴定鲍曼不动杆菌的生态位特异性适应
- 批准号:
10596620 - 财政年份:2022
- 资助金额:
$ 43.14万 - 项目类别:
Identifying niche specific adaptations in Acinetobacter baumannii
鉴定鲍曼不动杆菌的生态位特异性适应
- 批准号:
10449699 - 财政年份:2022
- 资助金额:
$ 43.14万 - 项目类别:














{{item.name}}会员




