Regulation of Intrinsic Caspofungin Resistance in C. neoformans
新型隐球菌内在卡泊芬净耐药性的调节
基本信息
- 批准号:9761969
- 负责人:
- 金额:$ 22.56万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-08-08 至 2021-07-31
- 项目状态:已结题
- 来源:
- 关键词:5&apos Untranslated RegionsAcquired Immunodeficiency SyndromeAmino Acid SequenceAmphotericin BAntifungal AgentsAntifungal TherapyArginineBindingC-terminalCaspofunginCell WallCellsCellular ImmunityCessation of lifeConsensusCryptococcosisCryptococcusCryptococcus neoformansCryptococcus neoformans infectionDataDefectDrug TargetingElementsExhibitsFluconazoleFlucytosineFoundationsFungal ProteinsFutureGeneticGenetic TranscriptionHypersensitivityImmunocompromised HostIn VitroIndustrial fungicideLeadLinkMeningitisMessenger RNAMethylationModelingMutagenesisMutationPathogenicityPatientsPharmaceutical PreparationsPolyadenylationPost-Transcriptional RegulationPredispositionProtein-Arginine N-MethyltransferaseProteinsRNA BindingRNA Recognition MotifRNA-Binding ProteinsRegulationResistanceResourcesRibosomesRoleSiteTestingTranslatingTranslationsTransplant RecipientsWorkechinocandin resistanceglucan synthasein vivoinhibitor/antagonistmRNA Stabilitymortalitymutantprotein Bresistance mechanismstressor
项目摘要
Abstract:
Cryptococcosis causes hundreds of thousands of deaths per year, mostly in resource-poor settings. C.
neoformans exhibits intrinsic resistance to echinocandin antifungals, eliminating this safe and effective class of
antifungal drug from the anti-cryptococcal arsenal. The mechanism of resistance is unknown, but it is
independent of drug target inhibition, as the target protein, the β-1,3-glucan synthase Fks1, is sensitive to the
drug. We have identified a regulator of caspofungin sensitivity in C. neoformans, Puf4, that controls the FKS1
mRNA at the level of stability, and a puf4 mutant is caspofungin resistant. Deletion putative post-translational
regulator of Puf4, the protein arginine methyltransferase (PRMT) Rmt5, confers hypersensitivity to
caspofungin, suggesting a role for arginine methylation in the regulation of Puf4 function and caspofungin
sensitivity. Our scientific premise is that Puf4 controls caspofungin sensitivity through post-transcriptional
regulation of the FKS1 mRNA, and that the ability of Puf4 to regulate FKS1 is dependent on its methylation
status. We will investigate the mechanism of Puf4 regulation including its binding to the FKS1 mRNA 5’ UTR
and the effect of that interaction on translation and mRNA stability (Aim 1). We will then investigate the role of
Puf4 methylation on its ability to regulate the FKS1 mRNA including the effect of rmt5 deletion on FKS1 post-
transcriptional regulation, the identification of methylation sites on Puf4 and the use of mutagenesis to
determine the consequence of methylation on effector function (Aim 2). PRMTs are known drug targets.
Determining the mechanism by which Rmt5 and its putative target Puf4 control caspofungin sensitivity may
lead to adjunctive therapies to potentiate the anti-cryptococcal activity of echinocandins.
文摘:
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 }}
John C Panepinto其他文献
John C Panepinto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('John C Panepinto', 18)}}的其他基金
Ribosome Heterogeneity in Cryptococcus neoformans
新型隐球菌的核糖体异质性
- 批准号:
10687190 - 财政年份:2021
- 资助金额:
$ 22.56万 - 项目类别:
Ribosome Heterogeneity in Cryptococcus neoformans
新型隐球菌的核糖体异质性
- 批准号:
10391779 - 财政年份:2021
- 资助金额:
$ 22.56万 - 项目类别:
Ribosome Heterogeneity in Cryptococcus neoformans
新型隐球菌的核糖体异质性
- 批准号:
10494146 - 财政年份:2021
- 资助金额:
$ 22.56万 - 项目类别:
Stress Responsive Reprogramming of Translating mRNA Pools in C. neoformans
新型隐球菌中翻译 mRNA 库的应激反应性重编程
- 批准号:
9913456 - 财政年份:2017
- 资助金额:
$ 22.56万 - 项目类别:
Stress Responsive Reprogramming of Translating mRNA Pools in C. neoformans
新型隐球菌中翻译 mRNA 库的应激反应性重编程
- 批准号:
10088140 - 财政年份:2017
- 资助金额:
$ 22.56万 - 项目类别:
Stress-Responsive RNA Regulons in Cryptococcus neoformans
新型隐球菌中的应激反应性 RNA 调节子
- 批准号:
8050342 - 财政年份:2011
- 资助金额:
$ 22.56万 - 项目类别:
Stress-Responsive RNA Regulons in Cryptococcus neoformans
新型隐球菌中的应激反应性 RNA 调节子
- 批准号:
8487347 - 财政年份:2011
- 资助金额:
$ 22.56万 - 项目类别:
Stress-Responsive RNA Regulons in Cryptococcus neoformans
新型隐球菌中的应激反应性 RNA 调节子
- 批准号:
8293351 - 财政年份:2011
- 资助金额:
$ 22.56万 - 项目类别:
Stress-Responsive RNA Regulons in Cryptococcus neoformans
新型隐球菌中的应激反应性 RNA 调节子
- 批准号:
8676642 - 财政年份:2011
- 资助金额:
$ 22.56万 - 项目类别:
Ccr4 in the maintenance of thermotolerance and pathogenicity of C. neoformans
Ccr4 在维持新型隐球菌的耐热性和致病性中的作用
- 批准号:
7261535 - 财政年份:2008
- 资助金额:
$ 22.56万 - 项目类别:
相似海外基金
Impact of alternative polyadenylation of 3'-untranslated regions in the PI3K/AKT cascade on microRNA
PI3K/AKT 级联中 3-非翻译区的替代多聚腺苷酸化对 microRNA 的影响
- 批准号:
573541-2022 - 财政年份:2022
- 资助金额:
$ 22.56万 - 项目类别:
University Undergraduate Student Research Awards
How do untranslated regions of cannabinoid receptor type 1 mRNA determine receptor subcellular localisation and function?
1 型大麻素受体 mRNA 的非翻译区如何决定受体亚细胞定位和功能?
- 批准号:
2744317 - 财政年份:2022
- 资助金额:
$ 22.56万 - 项目类别:
Studentship
MICA:Synthetic untranslated regions for direct delivery of therapeutic mRNAs
MICA:用于直接递送治疗性 mRNA 的合成非翻译区
- 批准号:
MR/V010948/1 - 财政年份:2021
- 资助金额:
$ 22.56万 - 项目类别:
Research Grant
Translational Control by 5'-untranslated regions
5-非翻译区域的翻译控制
- 批准号:
10019570 - 财政年份:2019
- 资助金额:
$ 22.56万 - 项目类别:
Translational Control by 5'-untranslated regions
5-非翻译区域的翻译控制
- 批准号:
10223370 - 财政年份:2019
- 资助金额:
$ 22.56万 - 项目类别:
Translational Control by 5'-untranslated regions
5-非翻译区域的翻译控制
- 批准号:
10455108 - 财政年份:2019
- 资助金额:
$ 22.56万 - 项目类别:
Synergistic microRNA-binding sites, and 3' untranslated regions: a dialogue of silence
协同的 microRNA 结合位点和 3 非翻译区:沉默的对话
- 批准号:
255762 - 财政年份:2012
- 资助金额:
$ 22.56万 - 项目类别:
Operating Grants
Analysis of long untranslated regions in Nipah virus genome
尼帕病毒基因组长非翻译区分析
- 批准号:
20790351 - 财政年份:2008
- 资助金额:
$ 22.56万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Search for mRNA elements involved in the compatibility between 5' untranslated regions and coding regions in chloroplast translation
寻找参与叶绿体翻译中 5 非翻译区和编码区之间兼容性的 mRNA 元件
- 批准号:
19370021 - 财政年份:2007
- 资助金额:
$ 22.56万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Post-transcriptional Regulation of PPAR-g Expression by 5'-Untranslated Regions
5-非翻译区对 PPAR-g 表达的转录后调控
- 批准号:
7131841 - 财政年份:2006
- 资助金额:
$ 22.56万 - 项目类别:














{{item.name}}会员




