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
基本信息
- 批准号:10569041
- 负责人:
- 金额:$ 21.25万
- 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:2022-02-08 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAmpicillinAnabolismAnimalsAntibiotic ResistanceAntibioticsBackBiocideCeftriaxoneCell WallCell physiologyCell surfaceCellsChemicalsComplementDataDesiccationESKAPE pathogensEnterococcusEnterococcus faecalisEnterococcus faeciumEnzymesExplosionExposure toGenesGenetic TranscriptionGenomeGoalsGrowthHabitatsHomologous GeneHospitalsHumanHypothetical ProteinInfectionInvestigationLactamsMedicineMicrobeMonobactamsMulti-Drug ResistanceNosocomial InfectionsPathway interactionsPenicillinsPeptidoglycanPhenotypePlayPredispositionProteinsReproducibilityResearchResistanceReverse Transcriptase Polymerase Chain ReactionRoleSideStarvationStructural ModelsTestingTimeWorkacronymsantimicrobial resistant infectionbeta-Lactam Resistancebeta-Lactamsbiological adaptation to stresscellular engineeringglobal healthgut microbiomeinhibitormembermodel organismmutantnovelpathogenprematureresilienceresistant strainscreeningtraittranscriptome sequencingtransposon sequencing
项目摘要
Project summary:
Enterococci are leading causes of multidrug resistant hospital acquired infection – the first E in
the ESKAPE acronym. We recently showed that the genus Enterococcus differs from its closest
extant ancestors in having evolved enhanced traits for survival, including to starvation and
desiccation, as well as to challenge by antibiotics and other biocides that target the cell surface.
That is, in diverging from its ancestors hundreds of millions of years ago, it gained features making
the cell more rugged and impermeable. We found that enterococci possess 10 genes that are
rare or do not exist outside of the genus. Moreover, we found that one of these, encoding a
hypothetical protein, contributes to intrinsic resistance to b-lactams – the largest class of
antibiotics used in human medicine. As a result of this intrinsic resistance, this antibiotic class has
been of limited use in controlling enterococcal infection. Here we propose to validate the
preliminary results implicating this gene, termed EF1909, in contributing to intrinsic b-lactam
resistance and more rigorously and fully assess the phenotype of cells engineered to lack this
feature. We additionally assess when in the growth cycle that EF1909 is expressed and determine
whether its presence/absence results in cell wall peptiglycan of altered composition as implicated
by its contribution to intrinsic b-lactam resistance. If we are able to substantiate the preliminary
indications of phenotype in this exploratory work, this would raise the prospect of then screening
for EF1909 inhibitors that would be predicted to render enterococci now vulnerable to inexpensive
and readily available b-lactam antibiotics. Rendering enterococci readily treatable by b-lactams
would be an advance of very high impact for global health.
项目概要:
肠球菌是多重耐药医院获得性感染的主要原因-第一个E
ESKAPE的缩写。我们最近发现,肠球菌属与其最接近的
现存的祖先进化出了增强的生存特征,包括饥饿和
干燥,以及通过抗生素和其他针对细胞表面的杀生物剂的挑战。
也就是说,在与数亿年前的祖先不同的过程中,
细胞更加坚固和不可渗透。我们发现肠球菌拥有10个基因,
罕见或不存在于属外。此外,我们发现,其中一个,编码一个
假设的蛋白质,有助于对β-内酰胺类的内在抗性-最大的一类
用于人类医学的抗生素。由于这种内在的耐药性,这类抗生素具有
在控制肠球菌感染方面用途有限。在这里,我们建议验证
初步结果表明,这种基因,称为EF 1909,有助于内在的b-内酰胺
抗性,并更严格和全面地评估缺乏这种抗性的细胞的表型
功能.我们还评估了EF 1909在生长周期中何时表达,并确定了
它的存在/不存在是否导致细胞壁肽聚糖的组成改变,
通过其对固有的β-内酰胺抗性的贡献。如果我们能证实初步证据
表型指标的探索性工作,这将提高然后筛选的前景
对于EF 1909抑制剂,预计将使肠球菌现在容易受到廉价的
和容易获得的β-内酰胺抗生素。使肠球菌易于通过β-内酰胺类药物治疗
将是对全球健康产生重大影响的一个进步。
项目成果
期刊论文数量(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:
10464409 - 财政年份:2022
- 资助金额:
$ 21.25万 - 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:
$ 21.25万 - 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:
$ 21.25万 - 项目类别:
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
- 批准号:
9151288 - 财政年份:2016
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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:
$ 21.25万 - 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:
$ 21.25万 - 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
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