Salmonella Genes Associated with Colonization of Specific Hosts

与特定宿主定植相关的沙门氏菌基因

• 批准号: 7938909
• 负责人: MICHAEL MCCLELLAND
• 金额: $ 44.05万
• 依托单位: VACCINE RESEARCH INSTITUTE OF SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7938909
• 关键词: Adhesions; Animal Experiments; Animal Model; Animals; Antibiotic Resistance; Biological Assay; Blood; Cells; Chickens; Cistrons; Code; Communities; Complement; DNA; Data; Dissection; Dose; Escherichia coli; Family suidae; Founder Generation; Funding; Genes; Genome; Genomics; Harvest; Human; Hybridization Array; In Vitro; Individual; Infection; Knock-out; Label; Laboratories; Lead; Libraries; Location; Marsupialia; Medical Economics; Methods; Modeling; Molecular; Monitor; Monodelphis; Mus; Mutate; Neomycin; Oligonucleotide Microarrays; Operon; Output; Phenotype; Phylogenetic Analysis; Play; Population Sizes; Predisposition; Process; Proteins; Radiation; Relative (related person); Reptiles; Research; Resources; Role; Salmonella; Salmonella enterica; Salmonella typhimurium; Sampling; Scheme; Specificity; Surveys; Technology; Testing; Time; Tissues; Turtles; Vertebrates; Virulence Factors; Wild Animals; animal tissue; base; design; fitness; genetic selection; genome sequencing; internal control; intraperitoneal; knockout gene; mutant; new technology; novel; novel therapeutics; pathogen; research study

Salmonella enterica serovar Typhimurium has a very broad host range and can colonize different Phyla. To date, only a small fraction of its genome has been surveyed for genes that differ in their contribution to colonization of different hosts. This project is designed to determine which Typhimurium mutants are unable to fully compete with wild type during colonization of three vertebrate host species, selected for their phylogenetic diversity and known susceptibility to Typhimurium infection: mouse, pig, and chicken. A pool of specific knockout mutants in every non-essential Typhimurium gene in vitro (~3900 knockouts) will be delivered intragastrically to the model animals. Short-term colonization in the gut will be monitored by dissection of host tissues at three days post infection. An oligonucleotide array with a novel design will be used to identify all mutants that become rarer during competitive colonization, indicating a role of that gene in the process. A novel fluctuation test will assure that only appropriate experiments will be applied to arrays. We have confirmed that the proposed assay detects almost all genes that are known to contribute to intraperitoneal and intragastric infection in the mouse. If the data suggest that a known colonization mechanism in one host may not be used in other hosts, this will be independently confirmed by testing single exemplar gene knockout mutants in these species. Novel host-restricted colonization mechanisms are beyond the scope of this two year project and will be studied, only if time and resources permit.

鼠伤寒沙门氏菌的宿主范围很广，可以定植于不同的菌群。到目前为止，只对其基因组中的一小部分进行了调查，以寻找对不同宿主的定植有不同贡献的基因。本项目旨在确定在三种脊椎动物宿主物种的定植过程中，哪些鼠伤寒沙门氏菌突变体无法与野生型完全竞争，这三种脊椎动物宿主物种的选择是因为它们的系统发育多样性和已知的对鼠伤寒沙门氏菌感染的易感性：小鼠、猪和鸡。在体外，每个非必需小鼠基因的特定敲除突变体库(约3900个敲除)将被灌胃内传递给模型动物。感染后三天将通过解剖宿主组织来监测肠道的短期定植情况。一个设计新颖的寡核苷酸阵列将被用来识别在竞争性殖民过程中变得更加罕见的所有突变，这表明该基因在这一过程中发挥了作用。一种新的波动测试将确保只对阵列应用适当的实验。我们已经证实，所提出的检测方法可以检测到几乎所有已知的导致小鼠腹膜和胃内感染的基因。如果数据表明，一个宿主中已知的定植机制可能不会在其他宿主中使用，这将通过测试这些物种中的单个样本基因敲除突变来独立确认。新的限制宿主的殖民机制超出了这个为期两年的项目的范围，只有在时间和资源允许的情况下才会进行研究。

项目成果

Live attenuated S. Typhimurium vaccine with improved safety in immuno-compromised mice.

• DOI: 10.1371/journal.pone.0045433
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Periaswamy B;Maier L;Vishwakarma V;Slack E;Kremer M;Andrews-Polymenis HL;McClelland M;Grant AJ;Suar M;Hardt WD
• 通讯作者: Hardt WD

Gene expression analysis of Salmonella enterica Enteritidis Nal(R) and Salmonella enterica Kentucky 3795 exposed to HCl and acetic acid in rich medium.

• DOI: 10.1089/fpd.2011.0984
• 发表时间: 2012-03
• 期刊: Foodborne pathogens and disease
• 影响因子: 2.8
• 作者: R. Joerger;C. Sartori;J. Frye;J. B. Turpin;C. Schmidt;Michael McClelland;S. Porwollik

Specific responses of Salmonella enterica to tomato varieties and fruit ripeness identified by in vivo expression technology.

• DOI: 10.1371/journal.pone.0012406
• 发表时间: 2010-08-31
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Noel JT;Arrach N;Alagely A;McClelland M;Teplitski M
• 通讯作者: Teplitski M

De novo pyrimidine synthesis is necessary for intestinal colonization of Salmonella Typhimurium in chicks.

• DOI: 10.1371/journal.pone.0183751
• 发表时间: 2017
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Yang HJ;Bogomolnaya L;McClelland M;Andrews-Polymenis H
• 通讯作者: Andrews-Polymenis H