Use of dominant repressor alleles for non-antibiotic selection in Yersinia pestis

使用显性阻遏等位基因进行鼠疫耶尔森氏菌的非抗生素选择

• 批准号: 7454945
• 负责人: James Gregory PHILLIPS
• 金额: $ 13.86万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7454945
• 关键词: Africa; Alleles; Americas; Amino Acids; Antibiotic Resistance; Antibiotics; Asia; Bacteria; Bioterrorism; Cells; Civilization; Class; Cloning Vectors; Commit; Disease; Disease Outbreaks; Engineering; Funding; Genes; Genetic; Genetic Engineering; Goals; Health; Human; Immunologist; Infection; Institution; Lead; Letters; Life; Metabolic; Methods; Numbers; Pathogenicity; Plague; Production; Repressor Proteins; Research; Research Personnel; Resistance; Resources; Risk; Septicemic plague; Series; Support of Research; System; Techniques; Testing; Today; United States; Vaccines; Virulence; Virulent; Work; Yersinia pestis; aerosolized; analog; base; genetic element; genetic manipulation; inhibitor/antagonist; innovation; laboratory facility; multidisciplinary; mutant; novel; novel vaccines; pandemic disease; pathogen; quorum sensing; tool; vaccine development

DESCRIPTION (provided by applicant): Yersinia pestis is the causative agent of bubonic, pneumonic and septicemic plague, and is currently a major concern as a potential bioterrorism weapon. An attack in the United States with aerosolized Y. pestis, which induces the fatal pneumonic form of the disease, would have severe consequences on human lives and the economy. Sporadic outbreaks of the plague also continue to occur naturally in Africa, Asia and the Americas. Strains of Y. pestis that are resistant to multiple antibiotics have recently been isolated, suggesting that natural outbreaks of plague may become more difficult to control. Currently, there are no effective vaccines to protect against Y. pestis, and unless antibiotics are administered immediately after infection, the disease is usually fatal. Research to identify new strategies to control Y. pestis will require genetic manipulation of the pathogen. However, most techniques in current use require the introduction of genetic elements that carry antibiotic resistance markers. Antibiotic resistant Y. pestis poses a health concern not only to researchers, but also as an enhanced risk if resistant strains are obtained by bioterrorists. This research seeks to test the main hypothesis that mutant repressor proteins will function as selectable markers by imparting resistance to potent metabolic inhibitors. These studies will provide new tools for genetic manipulation of Y. pestis that will lead to a better understand its pathogenicity as well as to the production of effective vaccines, without increasing virulence. The methods described here will also be applicable to other select agents of bioterrorism.

描述（由申请人提供）：

项目成果

Vectors for ligation-independent construction of lacZ gene fusions and cloning of PCR products using a nicking endonuclease.

• DOI: 10.1016/j.plasmid.2011.07.007
• 发表时间: 2011-09
• 期刊: Plasmid
• 影响因子: 2.6
• 作者: Oster CJ;Phillips GJ
• 通讯作者: Phillips GJ