Malter Kyle E, Dunbar Tiffany L, Westin Carl, Darin Emily, Alfaro Josefa Rivera, Shikuma Nicholas J
Department of Biology, San Diego State University, San Diego, California, USA.
Viral Information Institute, San Diego State University, San Diego, California, USA.
mBio. 2025 Feb 5;16(2):e0357324. doi: 10.1128/mbio.03573-24. Epub 2024 Dec 27.
Diverse marine animals undergo a metamorphic larval-to-juvenile transition in response to surface-bound bacteria. Although this host-microbe interaction is critical to establishing and maintaining marine animal populations, the functional activity of bacterial products and how they activate the host's metamorphosis program has not yet been defined for any animal. The marine bacterium stimulates the metamorphosis of a tubeworm called by producing a molecular syringe called metamorphosis-associated contractile structures (MACs). MACs stimulate metamorphosis by injecting a protein effector termed metamorphosis-inducing factor 1 (Mif1) into tubeworm larvae. Here, we show that MACs bind to tubeworm cilia and form visible pores on the cilia membrane surface, which are smaller and less numerous in the absence of Mif1. , Mif1 associates with eukaryotic lipid membranes and possesses phospholipase activity. MACs can also deliver Mif1 to human cell lines and cause parallel phenotypes, including cell surface binding, membrane disruption, calcium flux, and mitogen-activated protein kinase activation. Finally, MACs can also stimulate metamorphosis by delivering two unrelated membrane-disrupting proteins, MLKL and RegIIIɑ. Our findings demonstrate that membrane disruption by MACs and Mif1 is necessary for metamorphosis, connecting the activity of a bacterial protein effector to the developmental transition of a marine animal.
This research describes a mechanism wherein a bacterium prompts the metamorphic development of an animal from larva to juvenile form by injecting a protein that disrupts membranes in the larval cilia. Specifically, results show that a bacterial contractile injection system and the protein effector it injects form pores in larval cilia, influencing critical signaling pathways like mitogen-activated protein kinase and calcium flux, ultimately driving animal metamorphosis. This discovery sheds light on how a bacterial protein effector exerts its activity through membrane disruption, a phenomenon observed in various bacterial toxins affecting cellular functions, and elicits a developmental response. This work reveals a potential strategy used by marine organisms to respond to microbial cues, which could inform efforts in coral reef restoration and biofouling prevention. The study's insights into metamorphosis-associated contractile structures' delivery of protein effectors to specific anatomical locations highlight prospects for future biomedical and environmental applications.
多种海洋动物会因表面附着的细菌而经历从幼虫到幼体的变态转变。尽管这种宿主与微生物的相互作用对于海洋动物种群的建立和维持至关重要，但对于任何动物而言，细菌产物的功能活性以及它们如何激活宿主的变态程序尚未明确。海洋细菌通过产生一种称为变态相关收缩结构（MACs）的分子注射器来刺激一种称为 的管虫的变态。MACs通过将一种称为变态诱导因子1（Mif1）的蛋白质效应物注入管虫幼虫来刺激变态。在此，我们表明MACs与管虫纤毛结合并在纤毛膜表面形成可见的孔，在没有Mif1的情况下，这些孔更小且数量更少。此外，Mif1与真核生物脂质膜结合并具有磷脂酶活性。MACs还可以将Mif1递送至人类细胞系并导致类似的表型，包括细胞表面结合、膜破坏、钙通量和丝裂原活化蛋白激酶激活。最后，MACs还可以通过递送两种不相关的膜破坏蛋白MLKL和RegIIIɑ来刺激变态。我们的研究结果表明，MACs和Mif1引起的膜破坏对于 变态是必要的，将细菌蛋白质效应物的活性与海洋动物的发育转变联系起来。
本研究描述了一种机制，即一种细菌通过注入一种破坏幼虫纤毛膜的蛋白质来促使动物从幼虫发育为幼体形态。具体而言，结果表明一种细菌收缩注射系统及其注入的蛋白质效应物在幼虫纤毛中形成孔，影响丝裂原活化蛋白激酶和钙通量等关键信号通路，最终驱动动物变态。这一发现揭示了一种细菌蛋白质效应物如何通过膜破坏发挥其活性，这是在影响细胞功能的各种细菌毒素中观察到的一种现象，并引发发育反应。这项工作揭示了海洋生物用于响应微生物信号的一种潜在策略，这可能为珊瑚礁恢复和生物污损预防工作提供信息。该研究对变态相关收缩结构将蛋白质效应物递送至特定解剖位置的见解突出了未来生物医学和环境应用的前景。
