Clostridium perfringens Type B-D Virulence Plasmids
产气荚膜梭菌 B-D 型毒力质粒
基本信息
- 批准号:7009360
- 负责人:
- 金额:$ 40.24万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2003
- 资助国家:美国
- 起止时间:2003-07-01 至 2007-12-31
- 项目状态:已结题
- 来源:
- 关键词:Clostridium perfringensantibioticsbacterial cytopathogenic effectbacterial geneticsbacterial toxicologybacterial toxinsbioterrorism /chemical warfareclostridial infectiondisease /disorder modeldrug resistanceenzyme linked immunosorbent assaygel electrophoresisgene targetinggenetic straingenotypegoatsmicroorganism conjugationmicroorganism culturemutantphenotypeplasmidspolymerase chain reactionsheepsite directed mutagenesisvirulence
项目摘要
DESCRIPTION (provided by applicant): Clostridium perfringens type B, C, and D isolates have significant medical, veterinary, and biodefense importance. Several toxins (e.g. select agent "B" list epsilon toxin and beta toxin) expressed by type B-D isolates are encoded by genes present on large plasmids. The long-term goal of this project is to fully understand how those little-studied plasmids contribute to the virulence of type B-D isolates. To start progressing towards this goal, the following specific aims will be pursued: 1) constructing isogenic single and double toxin knock-out mutants in type B-D backgrounds using insertional mutagenesis approaches, 2) comparing the virulence of these newly-constructed isogenic mutants against their parents (and complemented mutants strains); this will be accomplished using in vivo and in vitro approaches that will evaluate enteric virulence (intestinal loop models), systemic virulence (intravenous injections of culture supernatants} and effects of an intraduodenal challenge mimicking the entire disease spectrum (i.e., both enteric and systemic disease), 3) using Aim #1 toxin mutants, which will carry virulence plasmids tagged with antibiotic resistance determinants, in mixed mating experiments to evaluate whether type B-D virulence plasmids can transfer between C. perfringens isolates via conjugation, 4) conducting phenotypic/genotypic analyses to evaluate the diversity of these isolates; these studies will involve examining type B-D isolates to determine how much beta- and/or epsilon-toxin (as appropriate) they produce, testing whether those toxin expression differences are related to promoter differences, determining if some type B-D isolates produce beta- or epsilon-toxin variants (as appropriate) with altered biologic activities, and examining the diversity of type B-D plasmid genomes using pulsed-field gel electrophoresis and microarray approaches, and 5)investigating non-toxin virulence plasmid functions by insertional inactivation approaches; if Aim #3 confirms that type B-D virulence plasmids can transfer via conjugation, Aim #5 will initially target putative DNA transfer genes on these plasmids. These studies are expected to provide critical information for developing improved vaccines/therapeutics against type B-D infections and for developing molecular assays to subtype these isolates, as necessary for forensic investigations in the event that type B-D isolates are deliberately released during a bioterrorism event.
描述(由申请人提供):B,C和D型分离株具有重大的医学,兽医和生物化的重要性。 B-D型分离株表达的几种毒素(例如,选择剂“ B”列表Epsilon毒素和β毒素)由大质粒上存在的基因编码。该项目的长期目标是充分了解那些研究较少的质粒如何有助于B-D型分离株的毒力。为了开始朝着这一目标迈进,将追求以下特定目标:1)使用插入诱变方法在B-D型背景中构建等源性单和双重毒素敲除突变体,2)比较这些新构建的等源性突变体的毒力与它们的毒力父母(和补充的突变体菌株);这将使用体内和体外方法来评估肠道毒力(肠环模型),全身性毒力(静脉注射培养上清液}以及模仿整个疾病谱(即肠内疾病和系统疾病,肠内疾病和系统疾病)的影响),3)使用AIM#1毒素突变体,它将在混合交配实验中携带用抗生素耐药性确定剂标记的毒力质粒,以评估B-D型毒力质粒是否可以通过共轭分离孢子分离,4)传导表型/基因型分析。评估这些分离株的多样性;这些研究将涉及检查B-D型分离株,以确定它们产生的β-和/或Epsilon toxin(适当),测试这些毒素表达差异是否与启动子差异有关,确定某些B-D分离株是否产生β-或Epsilon是否产生-Toxin变体(适当)随着生物学活性的改变,并使用脉冲场凝胶电泳和微阵列方法检查B-D质粒基因组的多样性,5)研究非毒素毒素质粒通过插入式失活方法进行研究;如果AIM#3证实B-D型毒力质粒可以通过共轭转移,AIM#5最初将靶向这些质粒上推定的DNA转移基因。预计这些研究将提供关键的信息,以开发针对B-D型感染的改进的疫苗/治疗剂,并为这些分离株开发分子测定,这对于在生物恐怖事件中故意释放出B-D型分离株的必要条件。
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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Bruce A Mc Clane其他文献
Bruce A Mc Clane的其他文献
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{{ truncateString('Bruce A Mc Clane', 18)}}的其他基金
NanI sialidase: Effects on Clostridium perfringens enterotoxin activity and contributions to C. perfringens type F infection
NanI 唾液酸酶:对产气荚膜梭菌肠毒素活性的影响以及对产气荚膜梭菌 F 型感染的贡献
- 批准号:
10055797 - 财政年份:2020
- 资助金额:
$ 40.24万 - 项目类别:
NanI sialidase: Effects on Clostridium perfringens enterotoxin activity and contributions to C. perfringens type F infection
NanI 唾液酸酶:对产气荚膜梭菌肠毒素活性的影响以及对产气荚膜梭菌 F 型感染的贡献
- 批准号:
10183154 - 财政年份:2020
- 资助金额:
$ 40.24万 - 项目类别:
Early interaction between clostridium perfringens epsilon toxin and host cells
产气荚膜梭菌ε毒素与宿主细胞之间的早期相互作用
- 批准号:
8233380 - 财政年份:2011
- 资助金额:
$ 40.24万 - 项目类别:
Early interaction between clostridium perfringens epsilon toxin and host cells
产气荚膜梭菌ε毒素与宿主细胞之间的早期相互作用
- 批准号:
7670079 - 财政年份:2009
- 资助金额:
$ 40.24万 - 项目类别:
Clostridium perfringens Type B-D Virulence Plasmids
产气荚膜梭菌 B-D 型毒力质粒
- 批准号:
7884390 - 财政年份:2003
- 资助金额:
$ 40.24万 - 项目类别:
Clostridium perfringens Type B-D Virulence Plasmids
产气荚膜梭菌 B-D 型毒力质粒
- 批准号:
6838204 - 财政年份:2003
- 资助金额:
$ 40.24万 - 项目类别:
Clostridium perfringens Type B-D Virulence Plasmids
产气荚膜梭菌 B-D 型毒力质粒
- 批准号:
8503578 - 财政年份:2003
- 资助金额:
$ 40.24万 - 项目类别:
Clostridium perfringens Type B-D Virulence Plasmids
产气荚膜梭菌 B-D 型毒力质粒
- 批准号:
6676995 - 财政年份:2003
- 资助金额:
$ 40.24万 - 项目类别:
Clostridium perfringens Type B-D Virulence Plasmids
产气荚膜梭菌 B-D 型毒力质粒
- 批准号:
7163698 - 财政年份:2003
- 资助金额:
$ 40.24万 - 项目类别:
Clostridium perfringens Type B-D Virulence Plasmids
产气荚膜梭菌 B-D 型毒力质粒
- 批准号:
8288751 - 财政年份:2003
- 资助金额:
$ 40.24万 - 项目类别:
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相似海外基金
Clostridium perfringens Type B-D Virulence Plasmids
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6838204 - 财政年份:2003
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