ACTA AND THE ACTIN BASED MOBILITY OF LISTERIA

Acta 和李斯特菌基于肌动蛋白的移动性

• 批准号: 2800078
• 负责人: AMY L DECATUR
• 金额: $ 2.5万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-14 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2800078
• 关键词: Listeria; actins; bacterial proteins; cell motility; dimer; gene mutation; polymerase chain reaction; polymerization; protein structure function; yeast two hybrid system

Listeria monocytogenes is a food-borne human and animal pathogen that causes serious illness in pregnant women and immunocompromised individuals, including AIDS patients. A key determinant of virulence for this intracellular pathogen is its ability to exploit the host cell actin cytoskeleton for intracellular movement and intercellular spread. The long-term objective of this proposal is to determine how the L. monocytogenes surface protein ActA initiates the accumulation of actin filaments around the bacterium, channels the polymerization of these actin filaments into a productive, motile force, and determines the rate of filament elongation and consequently the rate of bacterial movement. To this end, I will first isolate missense alleles and dominant negative alleles of actA and analyze the resulting mutant proteins in vivo and in vitro for their ability to nucleate actin, generate directional movement, and interact with host proteins. Second, I will test the hypothesis that a critical concentration of ActA is needed for the bacteria to initiate movement within host cells by altering the levels of actA expression. And finally, because recent biochemical and genetic evidence indicate that ActA forms homodimers, I will isolate actA mutants that are specifically defective in dimerization. These mutants will be used to determine whether dimer formation is necessary for ActA function, and if so, for what aspect of ActA function.

单核细胞增生李斯特菌是一种食源性人畜病原体