Function of the Klebsiella pneumoniae RND efflux systems
肺炎克雷伯菌 RND 外排系统的功能
基本信息
- 批准号:10649576
- 负责人:
- 金额:$ 23.85万
- 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:2022-06-17 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:AcidsAddressAffectAntibiotic ResistanceAntibioticsAntimicrobial ResistanceBacteriaBile fluidBiologyCell membraneCellsCenters for Disease Control and Prevention (U.S.)Chimeric ProteinsClassificationCommunitiesDataDevelopmentDiseaseDrug EffluxDrug resistanceEnvironmentEscherichia coliEvolutionFeedbackGene ExpressionGene ProteinsGenesGenetic TranscriptionGram-Negative BacteriaGrantGrowthHealthHomeostasisImpairmentIn VitroIndividualInfectionIronKlebsiella pneumoniaeLaboratoriesLarvaLinkMediatingMembraneMembrane FusionMetabolismMicrobial BiofilmsModelingMulti-Drug ResistanceNosocomial InfectionsPathogenesisPathogenicityPatientsPatternPersonsPhasePhenotypePhosphotransferasesPlayPneumoniaPore ProteinsProcessProductionProteinsProtonsPumpRepressionResearchResistanceRoleStructureSystemTestingTherapeuticTranscription InitiationVDAC1 geneVibrio choleraeVirulenceVirulentWorkWorld Health Organizationantimicrobialantimicrobial resistant infectionantiporterbiological adaptation to stresscapsulecell growthclinically relevantdesignefflux pumpenvironmental adaptationfollow-upglobal healthhealthcare-associated infectionshuman pathogenin vivomortalitymutantnovelnovel therapeutic interventionnovel therapeuticspathogenpathogenic bacteriaperiplasmresistance generesistant Klebsiella pneumoniaeresponsesensortraittranscriptomevirulence gene
项目摘要
PROJECT SUMMARY/ABSTRACT
The widespread use of antibiotics has driven the evolution and global dissemination of
resistance genes among pathogenic bacteria including Klebsiella pneumoniae which has evolved
resistance to all clinically relevant antibiotics. K. pneumoniae is leading cause of nosocomial
infections and has a high mortality rate and multiple drug resistance has made K. pneumoniae
infections difficult to treat. In addition to drug resistance, hypervirulent strains of K. pneumoniae that
cause community acquired invasive infections in healthy individuals have emerged globally. The
devastating consequences of K. pneumoniae infection, combined with the global dissemination of
resistance and virulence traits among K. pneumoniae, have led to K. pneumoniae being recognized
as an urgent health threat by the World Health Organization and the Centers for Disease Control.
This has highlighted the critical need for the development of new therapeutic approaches to treat
antimicrobial resistant infections. In this application we present preliminary data showing that multiple
drug efflux systems belonging to the Resistance-Nodulation-Sensing (RND) superfamily contribute to
the evolution of multiple antibiotic resistance in K. pneumoniae. In addition to their role in
antimicrobial resistance, RND efflux systems have also been shown to be required for multiple other
phenotypes including phenotypes required for virulence, but the mechanisms involved in this process
are largely unknown. In this proposal we will test the hypothesis that the K. pneumoniae RND efflux
systems are essential for multiple antibiotic resistance and pathogenesis. We propose two aims to
test our hypothesis. In aim 1 we will define the function of the individual K. pneumoniae RND efflux
systems in antimicrobial resistance and determine their effect on homeostasis. In aim 2 we will
investigate the contribution of the K. pneumoniae RND transporters to virulence-associated
phenotypes in vitro and in vivo pathogenic potential in the Galleria mellonella larvae infection model.
Completion of this work will define the function of the K. pneumoniae RND efflux systems in
antimicrobial resistance, biology and pathogenesis and illuminate novel aspects of K. pneumoniae
biology that may lead to the development of novel therapeutic approaches to treat antibiotic resistant
K. pneumoniae infections.
项目摘要/摘要
抗生素的广泛使用推动了细菌的进化和全球传播
包括肺炎克雷伯菌在内的病原菌的耐药基因
对所有临床上相关的抗生素都有耐药性。肺炎克雷伯菌是院内感染的主要原因
肺炎克雷伯菌具有较高的死亡率和多重耐药性。
感染很难治疗。除了抗药性外,肺炎克雷伯菌的超强毒力菌株
原因社区获得性侵袭性感染已在全球范围内出现。这个
肺炎克雷伯菌感染的破坏性后果,再加上肺炎克雷伯菌在全球的传播
肺炎克雷伯菌的耐药性和毒力特征导致肺炎克雷伯菌得到认可
被世界卫生组织和疾病控制中心列为紧迫的健康威胁。
这凸显了开发新的治疗方法的迫切需要。
抗菌素耐药性感染。在本申请中,我们提供的初步数据显示了多个
属于抗性-结瘤-传感(RND)超家族的药物外排系统有助于
肺炎克雷伯菌多重耐药性的演变。除了他们在
抗菌素耐药性,RND外排系统也被证明是多种其他
表型包括毒力所需的表型,但这一过程涉及的机制
在很大程度上是未知的。在这项建议中,我们将检验肺炎克雷伯菌RND外排的假设
系统在多重抗生素耐药和发病机制中是必不可少的。我们提出两个目标来
检验我们的假设。在目标1中,我们将定义单个肺炎克雷伯菌RND外排的功能
系统的抗菌素耐药性,并确定其对动态平衡的影响。在《目标2》中我们将
探讨肺炎克雷伯菌RND转运体对毒力相关的作用
梅隆沙门氏菌幼虫感染模型的体外表型和体内致病潜能。
这项工作的完成将确定肺炎克雷伯菌RND外排系统在
肺炎克雷伯菌的耐药性、生物学及致病机制
可能导致开发治疗抗生素耐药性的新治疗方法的生物学
肺炎克雷伯菌感染。
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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JAMES Edward BINA其他文献
JAMES Edward BINA的其他文献
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{{ truncateString('JAMES Edward BINA', 18)}}的其他基金
Function of the Klebsiella pneumoniae RND efflux systems
肺炎克雷伯菌 RND 外排系统的功能
- 批准号:
10525108 - 财政年份:2022
- 资助金额:
$ 23.85万 - 项目类别:
Role of cyclo(Phe-Pro) in Vibrio cholerae virulence factor production
环(Phe-Pro)在霍乱弧菌毒力因子产生中的作用
- 批准号:
8186812 - 财政年份:2011
- 资助金额:
$ 23.85万 - 项目类别:
Role of cyclo(Phe-Pro) in Vibrio cholerae virulence factor production
环(Phe-Pro)在霍乱弧菌毒力因子产生中的作用
- 批准号:
8423427 - 财政年份:2011
- 资助金额:
$ 23.85万 - 项目类别:
Role of cyclo(Phe-Pro) in Vibrio cholerae virulence factor production
环(Phe-Pro)在霍乱弧菌毒力因子产生中的作用
- 批准号:
8258229 - 财政年份:2011
- 资助金额:
$ 23.85万 - 项目类别:
Role of cyclo(Phe-Pro) in Vibrio cholerae virulence factor production
环(Phe-Pro)在霍乱弧菌毒力因子产生中的作用
- 批准号:
8449172 - 财政年份:2011
- 资助金额:
$ 23.85万 - 项目类别:
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