Characterization of lipid signaling altered by T3S effector AvrBsT

描述(申请人提供)：植物和动物的细菌病原体使用III型分泌(T3S)系统和效应蛋白底物来改变真核生理，以促进细菌繁殖和宿主定植。植物病原细菌中大量的T3S效应子(~20-30个蛋白质)表明，植物信号级联中的多个节点是靶标。然而，植物靶标的识别和这些T3S效应蛋白操纵植物生理的生化机制却知之甚少。广泛的表型研究支持这一概念，即许多T3S效应器抑制植物免疫系统以定植组织。这说明了基础防御反应和抗性(R)蛋白介导的先天免疫反应在控制植物界细菌感染结果方面的重要性。了解植物免疫是如何调节的，细菌病原体是如何操纵寄主的，这是预防和消除植物病害所必需的基础知识。该项目的长期目标是阐明植物如何整合脂质信号来应对细菌感染。两种保守的真核生物蛋白质--脂肪酶SOBER1和可能的载脂蛋白CIP--已经被鉴定出来，并被证明是植物天然免疫反应的重要调节因子。将利用拟南芥的病理系统进行全面的遗传和生化研究，以表征SOBER1和CIP底物的特异性，并确定这些蛋白在细菌感染过程中控制磷脂代谢和信号传递的机制。研究还将旨在确定病原体T3S效应因子AvrBsT扰乱受感染植物细胞内脂类平衡的生化机制。这项工作有望为植物控制脂代谢和响应病原体攻击的信号传递的生化机制提供基本的见解。越来越多的证据表明，在植物和动物中，脂代谢和免疫之间存在相互作用，这表明关于脂信号如何启动和终止的基础知识对于全面理解真核生物中免疫系统是如何调节的至关重要。 公共卫生相关性：了解植物免疫是如何调节的，细菌病原体是如何操纵宿主的，这是预防和消除植物疾病所必需的基本知识。

DESCRIPTION (provided by applicant): Bacterial pathogens of plant and animals use the type III secretion (T3S) system and effector protein substrates to alter eukaryotic physiology to promote bacterial multiplication and host colonization. The large repertoire of T3S effectors (~20-30 proteins) in plant pathogenic bacteria predicts that multiple nodes in plant signaling cascades are being targeted. The identity of the plant targets and the biochemical mechanisms by which these T3S effector proteins manipulate plant physiology however are poorly understood. Extensive phenotypic studies support the concept that many of the T3S effectors suppress the plant immune system to colonize tissues. This illuminates the importance of basal defense responses and resistance (R) protein-mediated innate immune responses in controlling the outcome of bacterial infections in the plant kingdom. Understanding how plant immunity is regulated and how bacterial pathogens manipulate their hosts is fundamental knowledge required for the prevention and elimination of plant disease. The long-term goal of this project is elucidate how plants integrate lipid signals to respond to bacterial infection. Two conserved eukaryotic proteins - SOBER1, a lipase and CIP, a putative apolipoprotein - have been identified and shown to be important regulators of innate immune responses in plants. Comprehensive genetic and biochemical studies will be performed using the Arabidopsis pathosystem to characterize SOBER1 and CIP substrate specificity and to determine the mechanisms by which these proteins control phospholipid metabolism and signaling during bacterial infection. Studies will also be aimed to determine the biochemical mechanisms by which the pathogen T3S effector AvrBsT perturbs lipid homeostasis within infected plant cells. This work is expected to provide fundamental insight to the biochemical mechanisms used by plants to control lipid metabolism and signaling in response to pathogen attack. The growing body of evidence suggesting an interplay between lipid metabolism and immunity in both plants and animals indicates that fundamental knowledge about how lipid signals are initiated and terminated will be essential to fully understand how the immune system is regulated in eukaryotes. PUBLIC HEALTH RELEVANCE: Understanding how plant immunity is regulated and how bacterial pathogens manipulate their hosts is fundamental knowledge required for the prevention and elimination of plant disease.