A Small Molecule That Blocks Salmonella Replication in Macrophages

阻止沙门氏菌在巨噬细胞中复制的小分子

• 批准号: 10312125
• 负责人: Corrella S Detweiler
• 金额: $ 19.25万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-07 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10312125
• 关键词: Affect; Anti-Bacterial Agents; Bacteria; Biological; Biology; Cell membrane; Cells; Chemicals; Colony-forming units; Constitution; Data; Development; Dose; Eukaryotic Cell; Future; Growth; Infection; Lead; Lighting; Lipids; Liposomes; Mammalian Cell; Measurement; Membrane; Membrane Biology; Membrane Fluidity; Microscopy; Molecular; Monitor; Morbidity - disease rate; Morphology; Mus; Phagosomes; Pharmaceutical Preparations; Property; Respiration; Salmonella; Salmonella typhimurium; Spleen; Structure; Testing; Toxic effect; Transmission Electron Microscopy; antimicrobial; base; drug development; experimental study; fluorescence imaging; human pathogen; improved; in vivo; macrophage; mitochondrial membrane; mortality; novel strategies; pathogen; pathogenic bacteria; pathogenic microbe; preference; prevent; screening; small molecule; tool; vesicular release; voltage

PROJECT SUMMARY How microbial pathogens evade host cellular defenses remains unclear. A full molecular understanding of host-pathogen interactions will aid in the development of new approaches to treat infection. There is a particular need to identify new classes of chemicals that target Gram-negative human pathogens. We therefore developed an in-cell, high content microscopy-based screening platform (called SAFIRE) that identifies compounds which prevent the accumulation of GFP- expressing Salmonella enterica serovar Typhimurium (S. Typhimurium) in macrophages. We are now at the stage of establishing compound mechanism of action, including defining why compounds enable the macrophage to survive while the bacterium is killed. The compound we propose to study, JD1, is not sufficiently developed to be a lead compound for drug development but is instead at the stage of basic biological discovery. These efforts may reveal new facets of host-pathogen biology, new targets for Gram-negative bacterial pathogens, and possibly identify a chemical that could be improved for use as an antimicrobial. 0

项目总结