Overcoming multidrug-resistance in hookworms
克服钩虫的多重耐药性
基本信息
- 批准号:10593148
- 负责人:
- 金额:$ 22.95万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-03-16 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:ABCB1 geneAccountingAddressAdultAmino AcidsAncylostoma (genus)Ancylostoma caninumAnthelminticsBindingBinding SitesBiological AssayCRISPR/Cas technologyCanis familiarisCommunicable DiseasesCutaneousDrug TargetingDrug or chemical Tissue DistributionDrug resistanceExhibitsFutureGenesGlycoproteinsGoalsHookwormsHumanKineticsKnowledgeLarvaLarva MigransLife Cycle StagesMammalsMapsMeasuresMediatingMessenger RNAMissionModelingMulti-Drug ResistanceNematodaOrthologous GeneOutcomeParasite resistanceParasitesPermeabilityPersonsPharmaceutical PreparationsPharmacologyPharmacotherapyPredispositionPropertyResistanceSiteSystemTechniquesTestingTissuesUnited StatesUnited States National Institutes of HealthVeterinariansZoonosesdisability-adjusted life yearsenteritishuman diseasein vivoinhibitorlactogenesisnovelpharmacologicpreventreceptorresponsetransmission process
项目摘要
Project Summary
Ancylostoma caninum causes cutaneous larva migrans and eosinophilic enteritis in
humans. The reason these human diseases cannot be eliminated is because the
parasite persists in the canine reservoir host. Multi-drug resistant isolates of A. caninum
are now circulating in the United States. In addition, specific life cycle stages (tissue-
dwelling larvae) are tolerant of anthelmintics even when the isolate is considered “drug
susceptible.”
Our hypothesis is that A. caninum evades drug treatment with permeability
glycoproteins (P-glycoproteins) that efflux anthelmintics and prevent them from binding
target receptors. In this application we propose to 1) identify the spectrum of
anthelmintics enhanced by P-glycoprotein inhibition in A. caninum, 2) record the
repertoire of Pgps expressed in response to each drug class, 3) map the precise tissues
where Pgps are expressed, 4) characterize the pharmacological profile of Aca-Pgp-11,
and 5) empirically determine regions of specific sites of nematode P-glycoprotein that
could be exploited. Our results will inform future studies testing the hypothesis that
nematode-specific P-glycoprotein inhibitors can be used to restore efficacy of multiple
existing anthelmintics and overcome drug resistant Ancylostoma.
项目摘要
犬钩虫引起皮肤幼虫移行症和嗜酸性肠炎,
人类这些人类疾病之所以不能被消除,是因为
寄生虫在犬类宿主体内持续存在。多药耐药菌株。caninum
现在在美国流传。此外,特定的生命周期阶段(组织-
寄生幼虫)对驱虫药耐受,即使该分离物被认为是“药物
易受影响”
我们的假设是A.犬用渗透性逃避药物治疗
排出驱虫剂并阻止其结合的糖蛋白(P-糖蛋白)
靶受体。在本申请中,我们提出:1)识别
在A.犬,2)记录
响应于每种药物类别表达的Pgps的库,3)绘制精确的组织
其中表示Pgp,4)表征Pgp-11的药理学特征,
和5)凭经验确定线虫P-糖蛋白的特异性位点的区域,
可能被利用。我们的研究结果将为未来的研究提供信息,
线虫特异性P-糖蛋白抑制剂可用于恢复多种抗线虫药物的功效。
现有的驱虫药和克服耐药性钩虫。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Repertoire of P-glycoprotein drug transporters in the zoonotic nematode Toxocara canis.
人畜共患毒素toxocara canis中P-糖蛋白药物转运蛋白的曲目。
- DOI:10.1038/s41598-023-31556-1
- 发表时间:2023-03-27
- 期刊:
- 影响因子:4.6
- 作者:Chelladurai, Jeba R. J. Jesudoss;Martin, Katy A.;Vardaxis, Pam;Reinemeyer, Craig;Vijayapalani, Paramasivan;Robertson, Alan P.;Brewer, Matthew T.
- 通讯作者:Brewer, Matthew T.
{{
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 }}
Matthew Brewer其他文献
Matthew Brewer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('Matthew Brewer', 18)}}的其他基金
Characterizing new nematode-specific drug targets to eliminate the reservoir for human toxocariasis
表征新的线虫特异性药物靶点以消除人类弓蛔虫病的储存库
- 批准号:
9882952 - 财政年份:2019
- 资助金额:
$ 22.95万 - 项目类别:
相似海外基金
Unraveling the Dynamics of International Accounting: Exploring the Impact of IFRS Adoption on Firms' Financial Reporting and Business Strategies
揭示国际会计的动态:探索采用 IFRS 对公司财务报告和业务战略的影响
- 批准号:
24K16488 - 财政年份:2024
- 资助金额:
$ 22.95万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Mighty Accounting - Accountancy Automation for 1-person limited companies.
Mighty Accounting - 1 人有限公司的会计自动化。
- 批准号:
10100360 - 财政年份:2024
- 资助金额:
$ 22.95万 - 项目类别:
Collaborative R&D
Accounting for the Fall of Silver? Western exchange banking practice, 1870-1910
白银下跌的原因是什么?
- 批准号:
24K04974 - 财政年份:2024
- 资助金额:
$ 22.95万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A New Direction in Accounting Education for IT Human Resources
IT人力资源会计教育的新方向
- 批准号:
23K01686 - 财政年份:2023
- 资助金额:
$ 22.95万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
An empirical and theoretical study of the double-accounting system in 19th-century American and British public utility companies
19世纪美国和英国公用事业公司双重会计制度的实证和理论研究
- 批准号:
23K01692 - 财政年份:2023
- 资助金额:
$ 22.95万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
An Empirical Analysis of the Value Effect: An Accounting Viewpoint
价值效应的实证分析:会计观点
- 批准号:
23K01695 - 财政年份:2023
- 资助金额:
$ 22.95万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Accounting model for improving performance on the health and productivity management
提高健康和生产力管理绩效的会计模型
- 批准号:
23K01713 - 财政年份:2023
- 资助金额:
$ 22.95万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
CPS: Medium: Making Every Drop Count: Accounting for Spatiotemporal Variability of Water Needs for Proactive Scheduling of Variable Rate Irrigation Systems
CPS:中:让每一滴水都发挥作用:考虑用水需求的时空变化,主动调度可变速率灌溉系统
- 批准号:
2312319 - 财政年份:2023
- 资助金额:
$ 22.95万 - 项目类别:
Standard Grant
New Role of Not-for-Profit Entities and Their Accounting Standards to Be Unified
非营利实体的新角色及其会计准则将统一
- 批准号:
23K01715 - 财政年份:2023
- 资助金额:
$ 22.95万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Improving Age- and Cause-Specific Under-Five Mortality Rates (ACSU5MR) by Systematically Accounting Measurement Errors to Inform Child Survival Decision Making in Low Income Countries
通过系统地核算测量误差来改善特定年龄和特定原因的五岁以下死亡率 (ACSU5MR),为低收入国家的儿童生存决策提供信息
- 批准号:
10585388 - 财政年份:2023
- 资助金额:
$ 22.95万 - 项目类别: