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Inhibitors of Type VI Sectretion in NIAID Priority Pathogens

NIAID 优先病原体中 VI 型分泌抑制剂

基本信息

批准号：
8233447
负责人：
STEPHEN LORY
金额：
$ 37.23万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-03-01 至 2014-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8233447
关键词：
Animal Model Animals Antibiotic Therapy Biological Biological Assay Biological Warfare Biology Bioterrorism Burkholderia Burkholderia mallei Burkholderia pseudomallei Categories Cells Chemicals Chromosomes Containment Cytoplasm Development Drug Kinetics Emerging Communicable Diseases Environment Eukaryotic Cell Gene Cluster Genetic Glanders Housing Infection Laboratories Lead Libraries Location Malleus Melioidosis Modification National Institute of Allergy and Infectious Disease New England Organism Pathway interactions Play Protein translocation Proteins Role Screening procedure Site Structure-Activity Relationship System Testing Therapeutic Therapeutic Agents Toxic effect Vaccines Virulence Virulence Factors Work antimicrobial antimicrobial drug base biodefense efficacy testing extracellular high throughput screening inhibitor/antagonist medical schools microorganism mortality novel pathogen pre-clinical programs protein complex therapeutic vaccine vaccine development

项目摘要

A number of pathogenic microorganisms, including, several NIAID Priority Pathogens, secrete virulence factors utilizing a novel pathway referred to as the type VI secretion system (T6SS). The main objective of this project is to develop inhibitors of T6SS that could lead to a new class of antimicrobial agents. Burkholderia thailandensis will be used to identify T6SS inhibitors compounds in a high throughput screen and these will be tested for interference with secretion in several category A-C select agents, including Burkholderia pseudomallei and Burkholderia mallei, causative agents of melioidosis and glanders, respectively. The candidate inhibitors of T6SS and their structural derivatives will be used in subsequent studies, which include demonstration of their efficacy in an animal model of melioidosis. The T6SS components, targeted by the active compounds will be identified. The work proposed in this project represents a logical pre-clinical development strategy for therapeutic agents targeting several agents of biological warfare and bioterrorism.

许多病原微生物，包括几种NIAID优先病原体，这些因子利用称为VI型分泌系统（T6 SS）的新途径。的主要目标这个项目是开发T6 SS的抑制剂，这可能导致一类新的抗菌剂。 Burkholderia thailandensis将用于在高通量筛选中鉴定T6 SS抑制剂化合物这些药物将在几种A-C类选择药物中进行分泌干扰试验，包括类鼻疽伯克霍尔德菌和鼻疽伯克霍尔德菌，类鼻疽和鼻疽的病原体，分别T6 SS的候选抑制剂及其结构衍生物将用于后续研究研究，包括在类鼻疽动物模型中证明其功效。T6SS 将鉴定活性化合物靶向的组分。本项目提出的工作代表了靶向多种药物的治疗药物的合理临床前开发策略，生物战和生物恐怖主义。