Lopez Miguel A, Saada Edwin A, Hill Kent L
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, USA.
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, USA Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, USA
Eukaryot Cell. 2015 Jan;14(1):104-12. doi: 10.1128/EC.00217-14. Epub 2014 Nov 21.
Sophisticated systems for cell-cell communication enable unicellular microbes to act as multicellular entities capable of group-level behaviors that are not evident in individuals. These group behaviors influence microbe physiology, and the underlying signaling pathways are considered potential drug targets in microbial pathogens. Trypanosoma brucei is a protozoan parasite that causes substantial human suffering and economic hardship in some of the most impoverished regions of the world. T. brucei lives on host tissue surfaces during transmission through its tsetse fly vector, and cultivation on surfaces causes the parasites to assemble into multicellular communities in which individual cells coordinate their movements in response to external signals. This behavior is termed "social motility," based on its similarities with surface-induced social motility in bacteria, and it demonstrates that trypanosomes are capable of group-level behavior. Mechanisms governing T. brucei social motility are unknown. Here we report that a subset of receptor-type adenylate cyclases (ACs) in the trypanosome flagellum regulate social motility. RNA interference-mediated knockdown of adenylate cyclase 6 (AC6), or dual knockdown of AC1 and AC2, causes a hypersocial phenotype but has no discernible effect on individual cells in suspension culture. Mutation of the AC6 catalytic domain phenocopies AC6 knockdown, demonstrating that loss of adenylate cyclase activity is responsible for the phenotype. Notably, knockdown of other ACs did not affect social motility, indicating segregation of AC functions. These studies reveal interesting parallels in systems that control social behavior in trypanosomes and bacteria and provide insight into a feature of parasite biology that may be exploited for novel intervention strategies.
复杂的细胞间通讯系统使单细胞微生物能够表现得如同多细胞实体，具备个体中不明显的群体水平行为。这些群体行为会影响微生物的生理机能，而潜在的信号传导途径被视为微生物病原体中的潜在药物靶点。布氏锥虫是一种原生动物寄生虫，在世界上一些最贫困的地区给人类带来了巨大痛苦和经济困难。在通过采采蝇媒介传播期间，布氏锥虫寄生于宿主组织表面，在表面上培养会使寄生虫聚集形成多细胞群落，其中单个细胞会根据外部信号协调它们的运动。基于其与细菌中表面诱导的群体运动的相似性，这种行为被称为“群体运动性”，它表明锥虫具有群体水平行为。控制布氏锥虫群体运动性的机制尚不清楚。在此我们报告，锥虫鞭毛中的一部分受体型腺苷酸环化酶（ACs）调节群体运动性。RNA干扰介导的腺苷酸环化酶6（AC6）敲低，或AC1和AC2的双重敲低，会导致超群体表型，但对悬浮培养中的单个细胞没有明显影响。AC6催化结构域的突变模拟了AC6敲低的效果，表明腺苷酸环化酶活性的丧失是导致该表型的原因。值得注意的是，其他ACs的敲低并不影响群体运动性，表明AC功能的分离。这些研究揭示了锥虫和细菌中控制群体行为的系统之间有趣的相似之处，并为寄生虫生物学的一个特征提供了见解，该特征可能被用于开发新的干预策略。
