Subproject 3 New Approaches to Treatment and Prevention of Antibiotic Resistant Infection
子项目3 治疗和预防抗生素耐药感染的新方法
基本信息
- 批准号:9151288
- 负责人:
- 金额:$ 33.84万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-09-01 至 2021-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAdvisory CommitteesAgricultureAntibiotic ResistanceAntibioticsChromosome MappingCollaborationsCollectionCrowdingDataEcologyEnterococcusEnterococcus faecalisEnterococcus faeciumEvolutionGenesGenus staphylococcusGoalsGovernmentGrowthHealthHospitalsHumanIn VitroInfectionInfection preventionLibrariesMedicineMulti-Drug ResistanceMusNational SecurityNosocomial InfectionsOperonPathway interactionsPatientsPreventionProductionReadingResourcesServicesStaphylococcus aureusSystemTechnologyTestingUrbanizationWorkanthropogenesiscomparative genomicsdesignimprovedin vivoinsightmembrane synthesismethicillin resistant Staphylococcus aureusnew therapeutic targetnext generationnovel strategiesnovel therapeuticspreventprogramspromoterprototypescreeningtool
项目摘要
Summary
Antibiotic resistance is an acute problem in US hospitals, and threatens every branch of medicine as
currently practiced. Antibiotic resistance is now even a national security concern. Staphylococcus
aureus (esp. MRSA) and the enterococci (esp. VRE) are among top causes of hospital infection that
are especially difficult to treat, because of multiple drug resistances and intrinsic hardiness. This
proposal, in collaboration and synergy with all other subprojects, attempts to respond to the national
challenge by building on advances made in the previous period of support, and focusing those
resources sharply on advancing tangible solutions to this crisis. Our overarching goals are to
improve the utility of antibiotic classes that currently exist, and to explore new therapeutic paradigms
for multidrug resistant infection. To achieve this goal, in this Subproject, we will pursue 2 Specific
Aims: 1) Identify impediments in MRSA/MSSA and VRE/VSE to antibiotic activity, and 2) Explore a
new paradigm for VRE infection prevention and treatment – Gut ecology management. This project
takes advantage of cutting-edge technologies and unique assets, including a crowd sourced strain
collection, to obtain new information from which new and better approaches for preventing and
treating multidrug resistant MRSA and VRE infections can be designed. We have pioneered the
application of comparative genomics to understand the origin and spread of antibiotic resistances
among enterococci; showing in the previous period, that anthropogenic factors such as the
urbanization of humans and the application of antibiotics in unprecedented levels, has driven their
evolution; and in collaboration with other subprojects, applied Tn-seq, to identify genes required for
S. aureus growth in vitro and in vivo as well as new drug targets. Each has been precedent-setting
in application to staphylococci and enterococci. These technologies now will be used to identify
impediments to target inhibition by antibiotics, and to inform the design of new antibiotics and
antibiotic potentiators. Further, a new treatment paradigm will be explored for prevention of VRE
colonization and infection. These results will provide critical information for optimizing the design of
new drugs and antibiotic potentiators; and new tools for improving the ecological management of
patients to reduce the likelihood and numbers of multidrug resistant infections. We believe this data
will be of substantial value in directly addressing the antibiotic resistance crisis that now exists.
摘要
抗生素耐药性是美国医院的一个严重问题,威胁着医学的每一个分支
目前正在练习。抗生素耐药性现在甚至是一个国家安全问题。葡萄球菌
金色的(尤指)MRSA)和肠球菌(尤其是VRE)是医院感染的主要原因之一
由于多重耐药性和内在的耐受性,尤其难以治疗。这
在与所有其他次级项目的协作和协同作用下,提案试图对国家
挑战,在上一次支持期间取得的进展的基础上再接再厉,并将重点放在
在这场危机的具体解决方案方面,我们将继续投入大量的资源。我们的首要目标是
提高现有抗生素类的效用,并探索新的治疗范例
用于多药耐药感染。为了实现这一目标,在这个子项目中,我们将追求2个具体的
目标:1)确定MRSA/MSSA和VRE/VSE中对抗生素活性的障碍,以及2)探索
VRE感染防治新范式--肠道生态管理。这个项目
利用尖端技术和独特的资产,包括众包压力
收集,以获得新的信息,从这些新的和更好的方法来预防和
治疗多重耐药的MRSA和VRE感染是可以设计的。我们开创了
应用比较基因组学研究抗生素耐药性的起源和传播
在肠球菌中;前一时期显示,人为因素,如
人类的城市化和抗生素的应用达到了前所未有的水平,推动了他们的
进化;并与其他子项目合作,应用TN-seq,以确定
金黄色葡萄球菌在体外和体内的生长以及新的药物靶点。每一次都开创了先例
适用于葡萄球菌和肠球菌。这些技术现在将被用来识别
抗生素靶向抑制的障碍,并为设计新的抗生素和
抗生素增强剂。此外,还将探索预防VRE的新治疗模式
殖民和感染。这些结果将为优化设计提供关键信息。
新的药物和抗生素增效剂;以及改善生态管理的新工具
减少患者耐多药感染的可能性和数量。我们相信这些数据
将在直接解决目前存在的抗生素耐药性危机方面具有实质性价值。
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 S Gilmore其他文献
Michael S Gilmore的其他文献
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{{ truncateString('Michael S Gilmore', 18)}}的其他基金
The Role of Enterococcus Unique Hypothetical EF1909 in Intrinsic β-lactam Resistance
肠球菌独特的假设 EF1909 在内在 β-内酰胺耐药性中的作用
- 批准号:
10569041 - 财政年份:2022
- 资助金额:
$ 33.84万 - 项目类别:
The Role of Enterococcus Unique Hypothetical EF1909 in Intrinsic β-lactam Resistance
肠球菌独特的假设 EF1909 在内在 β-内酰胺耐药性中的作用
- 批准号:
10464409 - 财政年份:2022
- 资助金额:
$ 33.84万 - 项目类别:
New understanding of LTA as a determinant of daptomycin susceptibility in VRE E. faecium
对 LTA 作为 VRE 屎肠球菌达托霉素敏感性决定因素的新认识
- 批准号:
9926227 - 财政年份:2019
- 资助金额:
$ 33.84万 - 项目类别:
New understanding of LTA as a determinant of daptomycin susceptibility in VRE E. faecium
对 LTA 作为 VRE 屎肠球菌达托霉素敏感性决定因素的新认识
- 批准号:
9810471 - 财政年份:2019
- 资助金额:
$ 33.84万 - 项目类别:
Molecular Basis for Ocular Surface Tropism in Conjunctivitis
结膜炎眼表向性的分子基础
- 批准号:
9264533 - 财政年份:2014
- 资助金额:
$ 33.84万 - 项目类别:
Molecular Basis for Ocular Surface Tropism in Conjunctivitis
结膜炎眼表向性的分子基础
- 批准号:
8670576 - 财政年份:2014
- 资助金额:
$ 33.84万 - 项目类别:
Identification of infection-critical S. aureus traits by TnSeq
通过 TnSeq 鉴定感染关键的金黄色葡萄球菌性状
- 批准号:
8660637 - 财政年份:2013
- 资助金额:
$ 33.84万 - 项目类别:
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