Insect Stage-Specific Adenylate Cyclases Regulate Social Motility in African Trypanosomes
Insect Stage-Specific Adenylate Cyclases Regulate Social Motility in African Trypanosomes
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DOI：
10.1128/ec.00217-14
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发表时间：
2015-01-01
期刊：
影响因子：
--
通讯作者：
Hill, Kent L.
中科院分区：
文献类型：
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作者：
Lopez, Miguel A.;Saada, Edwin A.;Hill, Kent L.
复杂的细胞-细胞通讯系统使单细胞微生物能够作为多细胞实体，能够在个体中不明显的群体水平行为。这些群体行为影响微生物生理，潜在的信号通路被认为是微生物病原体的潜在药物靶点。布鲁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造成严重的人类痛苦和经济困难。布鲁氏体在通过采采蝇媒介传播时生活在宿主组织表面，在表面培养使寄生虫聚集成多细胞群落，其中单个细胞根据外部信号协调其运动。这种行为被称为“社会运动性”，基于它与细菌表面诱导的社会运动性的相似性，它表明锥虫具有群体水平的行为能力。控制布氏体社会运动的机制尚不清楚。在这里，我们报告了锥虫鞭毛中受体型腺苷酸环化酶（ACs）的一个子集调节社会运动。RNA干扰介导的腺苷酸环化酶6 （AC6）的敲低，或AC1和AC2的双重敲低，会导致超社会表型，但对悬浮培养中的单个细胞没有明显的影响。AC6催化结构域的突变导致AC6敲低，表明腺苷酸环化酶活性的丧失是导致这种表型的原因。值得注意的是，敲除其他AC并不影响社会运动，表明AC功能的分离。这些研究揭示了控制锥虫和细菌社会行为的系统中有趣的相似之处，并提供了对寄生虫生物学特征的见解，这可能被用于开发新的干预策略。
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.