A bacterial membrane-disrupting protein stimulates animal metamorphosis
ABSTRACT 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...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2025-02-01
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| Series: | mBio |
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| Online Access: | https://journals.asm.org/doi/10.1128/mbio.03573-24 |
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| author | Kyle E. Malter Tiffany L. Dunbar Carl Westin Emily Darin Josefa Rivera Alfaro Nicholas J. Shikuma |
| author_facet | Kyle E. Malter Tiffany L. Dunbar Carl Westin Emily Darin Josefa Rivera Alfaro Nicholas J. Shikuma |
| author_sort | Kyle E. Malter |
| collection | DOAJ |
| description | ABSTRACT 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 Pseudoalteromonas luteoviolacea stimulates the metamorphosis of a tubeworm called Hydroides elegans 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. In vitro, 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 Hydroides metamorphosis, connecting the activity of a bacterial protein effector to the developmental transition of a marine animal.IMPORTANCEThis 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. |
| format | Article |
| id | doaj-art-8b4ef7f61bdb4a4e80e6e321c87114e3 |
| institution | Kabale University |
| issn | 2150-7511 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj-art-8b4ef7f61bdb4a4e80e6e321c87114e32025-02-05T14:00:48ZengAmerican Society for MicrobiologymBio2150-75112025-02-0116210.1128/mbio.03573-24A bacterial membrane-disrupting protein stimulates animal metamorphosisKyle E. Malter0Tiffany L. Dunbar1Carl Westin2Emily Darin3Josefa Rivera Alfaro4Nicholas J. Shikuma5Department of Biology, San Diego State University, San Diego, California, USADepartment of Biology, San Diego State University, San Diego, California, USADepartment of Biology, San Diego State University, San Diego, California, USADepartment of Biology, San Diego State University, San Diego, California, USADepartment of Biology, San Diego State University, San Diego, California, USADepartment of Biology, San Diego State University, San Diego, California, USAABSTRACT 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 Pseudoalteromonas luteoviolacea stimulates the metamorphosis of a tubeworm called Hydroides elegans 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. In vitro, 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 Hydroides metamorphosis, connecting the activity of a bacterial protein effector to the developmental transition of a marine animal.IMPORTANCEThis 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.https://journals.asm.org/doi/10.1128/mbio.03573-24metamorphosiscontractile injection systemeffectorpore-forming toxinciliatoxin |
| spellingShingle | Kyle E. Malter Tiffany L. Dunbar Carl Westin Emily Darin Josefa Rivera Alfaro Nicholas J. Shikuma A bacterial membrane-disrupting protein stimulates animal metamorphosis mBio metamorphosis contractile injection system effector pore-forming toxin cilia toxin |
| title | A bacterial membrane-disrupting protein stimulates animal metamorphosis |
| title_full | A bacterial membrane-disrupting protein stimulates animal metamorphosis |
| title_fullStr | A bacterial membrane-disrupting protein stimulates animal metamorphosis |
| title_full_unstemmed | A bacterial membrane-disrupting protein stimulates animal metamorphosis |
| title_short | A bacterial membrane-disrupting protein stimulates animal metamorphosis |
| title_sort | bacterial membrane disrupting protein stimulates animal metamorphosis |
| topic | metamorphosis contractile injection system effector pore-forming toxin cilia toxin |
| url | https://journals.asm.org/doi/10.1128/mbio.03573-24 |
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