Differential Effects of TcdB1 and TcdB2 in C. difficile disease
Differential Effects of TcdB1 and TcdB2 in C. difficile disease
批准号:
8945312
负责人:
Jimmy D. Ballard
金额:
$18.5万
依托单位国家:
美国
项目类别:
财政年份:
2015
资助国家:
美国
项目状态:
已结题
起止时间:
2015-08-07 至 2020-01-31
关键词:
AccountingAddressAntibiotic ResistanceAntibodiesCellsCharacteristicsClostridium difficileDataDeveloped CountriesDiseaseDisease OutcomeEndocytosisEpitopesEventHealthHomologous GeneHospitalsHumanImmuneImmune responseImmunityIn VitroInfectionInflammationIntoxicationMapsMolecularPatientsProductionPublishingRecurrenceResearchTherapeuticTherapeutic antibodiesTissuesToxic effectToxinTropismVaccinesVariantVirulenceVirulence FactorsVirulentbasecytotoxiccytotoxicityexperiencegastrointestinalin vivoinsightmortalityneutralizing antibodypathogenpreventpublic health relevancereceptorreceptor bindingresearch studytissue tropism
中文摘要
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英文摘要
DESCRIPTION (provided by applicant): Clostridium difficile is a leading cause of hospital-acquired illness in developed countries. Treating C. difficile infection (CDI) is complicated by antibiotic resistance, recurrence (RCDI), and hypervirulence of emerging strains that produce a highly toxic variant of TcdB. TcdB is a major C. difficile virulence factor that contributes to gastrointestinal damage, inflammation, and systemic damage. In these studies experiments will characterize the differences between the historical and milder form of TcdB (TcdB1) and the hypertoxic TcdB2. Published and preliminary data from our group shows that TcdB2 has a broader tropism and is more cytotoxic than TcdB1. In addition, antibodies to TcdB1 do not cross-neutralize TcdB2, suggesting that current vaccines and therapeutic antibodies targeting TcdB may not provide broad protection against multiple strains of C. difficile. The study will examine molecular differences between TcdB1 and TcdB2 to determine how these impact cellular intoxication, antigenicity, and influence RCDI. Aim 1 will characterize the differences in
dual-receptor interactions between TcdB1 and TcdB2, assess how this impacts endocytosis, and identify key residues that influence these events. Aim 2 will explore a mechanism through which TcdB2 cloaks neutralizing epitopes which are otherwise exposed in TcdB1. Experiments in aim 3 of this project will determine how the differences in TcdB1 and TcdB2 predispose patients to RCDI. The results from this project will provide the first insights into the differentil effects of TcdB1 and TcdB2 and the impact of TcdB2's heightened toxicity and altered antigenicity on the emergence of hypervirulent strains of C. difficile.
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会议论文
Oklahoma C. difficile U19 Challenge Core
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批准号:10625174
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项目类别:
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资助金额:$7.32万
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财政年份:2023
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负责人:Jimmy D. Ballard
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依托单位:
Enhancing C. difficile vaccination in the context of TcdB-mediated immunosuppression.
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批准号:10625175
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项目类别:
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资助金额:$35.61万
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财政年份:2023
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负责人:Jimmy D. Ballard
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依托单位:
Oklahoma CMP&I Administrative Core
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批准号:10554352
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项目类别:
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资助金额:$55.87万
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财政年份:2020
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负责人:Jimmy D. Ballard
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依托单位:
Oklahoma Center for Microbial Pathogenesis and Immunity
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批准号:10341201
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项目类别:
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资助金额:$216.67万
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财政年份:2020
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负责人:Jimmy D. Ballard
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依托单位:
Oklahoma Center for Microbial Pathogenesis and Immunity
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批准号:10554351
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项目类别:
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资助金额:$215.74万
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财政年份:2020
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负责人:Jimmy D. Ballard
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依托单位:
Oklahoma CMP&I Administrative Core
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批准号:10341202
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项目类别:
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资助金额:$58.35万
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财政年份:2020
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负责人:Jimmy D. Ballard
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依托单位:
Differential Effects of TcdB1 and TcdB2 in C. difficile disease
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批准号:10094178
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项目类别:
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资助金额:$43.23万
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财政年份:2015
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负责人:Jimmy D. Ballard
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依托单位:
Differential Effects of TcdB1 and TcdB2 in C. difficile disease
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批准号:10331732
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项目类别:
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资助金额:$43.23万
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财政年份:2015
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负责人:Jimmy D. Ballard
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依托单位:
Differential Effects of TcdB1 and TcdB2 in C. difficile disease
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批准号:10548849
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项目类别:
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资助金额:$43.23万
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财政年份:2015
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负责人:Jimmy D. Ballard
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依托单位:
Edema Toxin Suppression of Immune Responses During Anthrax Disease
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批准号:7695606
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项目类别:
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资助金额:$34.41万
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财政年份:2009
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负责人:Jimmy D. Ballard
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依托单位:
Pilot Project Program
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批准号:7696181
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项目类别:
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资助金额:$15.34万
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财政年份:2009
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负责人:Jimmy D. Ballard
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依托单位:
Scientific Core: Bacillus anthracis Anthrax Toxin Core
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批准号:7696197
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项目类别:
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资助金额:$12.67万
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财政年份:2009
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负责人:Jimmy D. Ballard
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依托单位:
Systemic events in Clostridium difficile associated disease
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批准号:7502013
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项目类别:
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资助金额:$36.42万
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财政年份:2007
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负责人:Jimmy D. Ballard
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依托单位:
Systemic events in Clostridium difficile associated disease
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批准号:7669173
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项目类别:
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资助金额:$36.42万
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财政年份:2007
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负责人:Jimmy D. Ballard
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依托单位:
Systemic events in Clostridium difficile associated disease
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批准号:7899938
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项目类别:
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资助金额:$36.42万
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财政年份:2007
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负责人:Jimmy D. Ballard
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依托单位:
Systemic events in Clostridium difficile associated disease
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批准号:7316547
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项目类别:
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资助金额:$36.42万
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财政年份:2007
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负责人:Jimmy D. Ballard
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依托单位:
Impact of Anthrax Toxin on Embryonic Development
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批准号:6672327
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项目类别:
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资助金额:$29.06万
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财政年份:2003
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负责人:Jimmy D. Ballard
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依托单位:
The Impact of Anthrax Toxin on Embryonic Development
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批准号:6763255
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项目类别:
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资助金额:$29.1万
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财政年份:2003
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负责人:Jimmy D. Ballard
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依托单位:
Edema Toxin Suppression of Immune Responses During Anthrax Disease
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批准号:8716418
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项目类别:
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资助金额:$36.58万
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财政年份:--
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负责人:Jimmy D. Ballard
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依托单位:
Edema Toxin Suppression of Immune Responses During Anthrax Disease
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批准号:8379006
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项目类别:
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资助金额:$33.26万
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财政年份:--
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负责人:Jimmy D. Ballard
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依托单位:
海外基金