Direct Inhibition of Antrhax Toxin Action

直接抑制炭疽毒素作用

• 批准号: 7642986
• 负责人: ROBERT JOHN COLLIER
• 金额: $ 78.77万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7642986
• 关键词: Animal Model; Anthrax Attack; Anthrax disease; Bacillus anthracis; Biological Assay; Bioterrorism; Cessation of life; Glutamic Acid; Immunization; Infection; Injection of therapeutic agent; Laboratories; Lead; Mus; Rodent; Testing; Therapeutic Intervention; Toxic effect; Toxin; Vaccine Therapy; Virulence Factors; anthrax toxin; base; capsule; experience; falls; high throughput screening; inhibitor/antagonist; macrophage; molecular mass; nonhuman primate; novel therapeutics

Besides exposing our general vulnerability to bioterrorism, the anthrax attacks of the fall of 2001 alerted the nation to the need to develop therapies and vaccines against Bacillus anthracis. B. anthracis produces two major virulence factors--an antiphagocytic poly-D-glutamic acid capsule and a tripartite toxin. Injection of the purified toxin causes rapid death of sensitive rodents and non-human primates, and immunization against the toxin protects against infection. Thus it is generally believed that death from anthrax infections results from the effects of the toxin. As a step towards developing new therapeutic interventions for anthrax, we propose to use a high-throughput screen to identify low molecular mass compounds that inhibit the action of anthrax toxin at the cellular level. We have developed a sensitive assay based on the effect of this toxin on mouse macrophages. Building on the experience of the Collier laboratory in studying anthrax toxin, we will characterize the most promising inhibitors found, to determine the specific step in toxin action that each inhibits. Lead compounds with low toxicity will be considered for testing in animal models of toxin action.

除了暴露了我们在生物恐怖主义面前的普遍脆弱性，2001年秋天的炭疽袭击也警醒了