Cytoplasmic contractile injection systems mediate cell death in Streptomyces.

Cytoplasmic contractile injection systems mediate cell death in Streptomyces.
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DOI:
10.1038/s41564-023-01341-x
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发表时间:
2023-04
影响因子:
28.3
通讯作者:
Pilhofer, Martin
Pilhofer, Martin
中科院分区:
生物学1区
文献类型:
--
作者:
Casu, Bastien;Sallmen, Joseph W.;Schlimpert, Susan;Pilhofer, Martin

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收缩注射系统(CIS)是一种噬菌体尾状结构,介导细菌细胞与细胞之间的相互作用。虽然CIS在不同的细菌门中高度丰富,但对革兰氏阳性生物中具有代表性的基因簇的研究仍然很少。在这里,我们描述了革兰氏阳性多细胞模式生物天蓝色链霉菌的CIS,并表明与大多数其他CIS不同的是,S.coelicolor CIS(CISSc)介导了细胞在应激反应中的死亡并影响细胞的发育。CisSc在营养菌丝的细胞质中表达,不释放到培养基中。我们的低温电子显微镜结构使非收缩和荧光标记的CISSc组件的工程成为可能。冷冻电子断层扫描显示,CisSc的收缩与细胞完整性降低有关。荧光显微镜进一步显示,当遇到不同类型的应激时,功能性CISSc介导细胞死亡。CisSc功能缺失对菌丝分化和次生代谢物的产生有影响。最后,我们鉴定了三个可能的效应蛋白,当没有这些蛋白时,它们就会复制到其他CisSc突变体上。我们的结果为革兰氏阳性生物中的CIS提供了新的功能见解,并为研究新的细胞内角色提供了一个框架,包括多细胞细菌中受调控的细胞死亡和生命周期进展。对革兰氏阳性多细胞模式生物天蓝色链霉菌的收缩注射系统(CIS)的表征发现,CIS介导了细胞对影响细胞发育的应激反应的死亡。
Contractile injection systems (CIS) are bacteriophage tail-like structures that mediate bacterial cell–cell interactions. While CIS are highly abundant across diverse bacterial phyla, representative gene clusters in Gram-positive organisms remain poorly studied. Here we characterize a CIS in the Gram-positive multicellular model organism Streptomyces coelicolor and show that, in contrast to most other CIS, S. coelicolor CIS (CISSc) mediate cell death in response to stress and impact cellular development. CISSc are expressed in the cytoplasm of vegetative hyphae and are not released into the medium. Our cryo-electron microscopy structure enabled the engineering of non-contractile and fluorescently tagged CISSc assemblies. Cryo-electron tomography showed that CISSc contraction is linked to reduced cellular integrity. Fluorescence light microscopy furthermore revealed that functional CISSc mediate cell death upon encountering different types of stress. The absence of functional CISSc had an impact on hyphal differentiation and secondary metabolite production. Finally, we identified three putative effector proteins, which when absent, phenocopied other CISSc mutants. Our results provide new functional insights into CIS in Gram-positive organisms and a framework for studying novel intracellular roles, including regulated cell death and life-cycle progression in multicellular bacteria. Characterization of a contractile injection system (CIS) in the Gram-positive multicellular model organism Streptomyces coelicolor finds that CIS mediate cell death in response to stress that impacts cellular development.
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期刊: Science (New York, N.Y.)
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