Differential Effects of TcdB1 and TcdB2 in C. difficile disease
TcdB1 和 TcdB2 在艰难梭菌疾病中的不同作用
基本信息
- 批准号:10548849
- 负责人:
- 金额:$ 43.23万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-08-07 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:AccountingAddressAnimal ModelAntigen PresentationAntigensAttenuatedBacterial ToxinsBindingBiochemicalCRISPR/Cas technologyCell CommunicationCell Surface ReceptorsCellsCessation of lifeCharacteristicsClostridium difficileComplementarity Determining RegionsDataDevelopmentDiseaseEndocytosisEndonuclease IEpidemicFrequenciesGenesGlucosyltransferaseHamstersHospitalsHumanHumoral ImmunitiesImmunologic MemoryImmunosuppressionIn VitroInfectionIntoxicationInvestigationKnowledgeMediatingMemory B-LymphocyteMolecularMonomeric GTP-Binding ProteinsMutationPathogenesisPatientsPenetrationPeptidesProteinsPublishingReceptor CellRelapseReportingReproduction sporesResearchRoleSeverity of illnessSystemTestingTherapeuticTimeToxic effectToxinTropismUnited StatesVaccinationVaccine AntigenVariantVirulenceVirulence FactorsWorkcell typecytotoxicityexperimental studygastrointestinalimmunogenicityin vivoinhibitorinsightmouse modelmutantnovelpathogenpreventprogramsreceptorreceptor bindingresponsetissue tropism
项目摘要
ABSTRACT
The most recent reports indicate Clostridioides difficile is the cause of over 400,000 cases of
gastrointestinal illness and nearly 30,000 deaths annually. A major factor in the virulence of C.
difficile is TcdB, an intracellular bacterial toxin that glucosylates small GTPases in targeted cells.
Our studies focus on determining the critical differences in TcdB1 and TcdB2, the two major
variants of TcdB. TcdB1 is produced by historical strains of C. difficile and TcdB2 is produced by
hypervirulent/epidemic strains of C. difficile. Understanding how these two forms of TcdB, which
share 92% identity, differ in critical steps in intoxication and immunogenicity provides insight into
underlying differences in virulence between historical and epidemic strains of C. difficile. Several
studies, including many from our group, have found that TcdB1 and TcdB2 differ in their
interactions with target cells, tropism, cytotoxicity, and immunogenicity. The objective of our work
is to identify and characterize the underlying molecular and cellular details of the factors
accounting for these differences in TcdB1 and TcdB2 activity. To continue this line of
investigation, three specific aims to i) Determine the underlying differences in the molecular
mechanism of TcdB1 and TcdB2 receptor binding and cell penetration, ii) Determine if TcdB2
subverts antigen presentation and limits humoral immunity to co-administered vaccine antigen
TcdB2Δ1769-1787, and iii) Construct and test strains of C. difficile expressing mutants of TcdB1
and TcdB2 will be pursued. These studies will provide further insight into the differences in TcdB1
and TcdB2, determine the contribution of TcdB to ineffective immune memory leading to relapse,
and test hypotheses related to specific TcdB functional activities in the context of C. difficile
infection. Overall, the findings from this work will enhance our understanding of C. difficile disease
at multiple levels and provide information needed to prevent and treat this serious human illness.
摘要
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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Jimmy D. Ballard其他文献
A toxin contest
一场毒素竞赛
- DOI:
10.1038/467665a - 发表时间:
2010-10-06 - 期刊:
- 影响因子:48.500
- 作者:
Jimmy D. Ballard - 通讯作者:
Jimmy D. Ballard
CSPG4-dependent cytotoxicity for emC. difficile/em TcdB is influenced by extracellular calcium and chondroitin sulfate
艰难梭菌 TcdB 对 emC 的 CSPG4 依赖性细胞毒性受细胞外钙和硫酸软骨素的影响
- DOI:
10.1128/msphere.00094-24 - 发表时间:
2024-03-12 - 期刊:
- 影响因子:3.100
- 作者:
D. Annie Doyle;Paul L. DeAngelis;Jimmy D. Ballard;Sarah E. F. D'Orazio - 通讯作者:
Sarah E. F. D'Orazio
Critical intermediate steps in <em>Clostridium sordellii</em> lethal toxin-induced apoptosis
- DOI:
10.1016/j.bbrc.2007.09.073 - 发表时间:
2007-11-30 - 期刊:
- 影响因子:
- 作者:
Daniel E. Voth;Jimmy D. Ballard - 通讯作者:
Jimmy D. Ballard
A toxin contest
一场毒素竞赛
- DOI:
10.1038/467665a - 发表时间:
2010-10-06 - 期刊:
- 影响因子:48.500
- 作者:
Jimmy D. Ballard - 通讯作者:
Jimmy D. Ballard
Jimmy D. Ballard的其他文献
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{{ truncateString('Jimmy D. Ballard', 18)}}的其他基金
Oklahoma C. difficile U19 Challenge Core
俄克拉荷马州艰难梭菌 U19 挑战核心
- 批准号:
10625174 - 财政年份:2023
- 资助金额:
$ 43.23万 - 项目类别:
Enhancing C. difficile vaccination in the context of TcdB-mediated immunosuppression.
在 TcdB 介导的免疫抑制背景下加强艰难梭菌疫苗接种。
- 批准号:
10625175 - 财政年份:2023
- 资助金额:
$ 43.23万 - 项目类别:
Oklahoma Center for Microbial Pathogenesis and Immunity
俄克拉荷马州微生物发病机制和免疫中心
- 批准号:
10341201 - 财政年份:2020
- 资助金额:
$ 43.23万 - 项目类别:
Oklahoma Center for Microbial Pathogenesis and Immunity
俄克拉荷马州微生物发病机制和免疫中心
- 批准号:
10554351 - 财政年份:2020
- 资助金额:
$ 43.23万 - 项目类别:
Differential Effects of TcdB1 and TcdB2 in C. difficile disease
TcdB1 和 TcdB2 在艰难梭菌疾病中的不同作用
- 批准号:
10094178 - 财政年份:2015
- 资助金额:
$ 43.23万 - 项目类别:
Differential Effects of TcdB1 and TcdB2 in C. difficile disease
TcdB1 和 TcdB2 在艰难梭菌疾病中的不同作用
- 批准号:
8945312 - 财政年份:2015
- 资助金额:
$ 43.23万 - 项目类别:
Differential Effects of TcdB1 and TcdB2 in C. difficile disease
TcdB1 和 TcdB2 在艰难梭菌疾病中的不同作用
- 批准号:
10331732 - 财政年份:2015
- 资助金额:
$ 43.23万 - 项目类别:
Edema Toxin Suppression of Immune Responses During Anthrax Disease
炭疽病期间水肿毒素抑制免疫反应
- 批准号:
7695606 - 财政年份:2009
- 资助金额:
$ 43.23万 - 项目类别:
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