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Communication via extracellular vesicles enhances viral infection of a cosmopolitan alga

Abstract

Communication between microorganisms in the marine environment has immense ecological impact by mediating trophic-level interactions and thus determining community structure1. Extracellular vesicles (EVs) are produced by bacteria2,3, archaea4, protists5 and metazoans, and can mediate pathogenicity6 or act as vectors for intercellular communication. However, little is known about the involvement of EVs in microbial interactions in the marine environment7. Here we investigated the signalling role of EVs produced during interactions between the cosmopolitan alga Emiliania huxleyi and its specific virus (EhV, Phycodnaviridae)8, which leads to the demise of these large-scale oceanic blooms9,10. We found that EVs are highly produced during viral infection or when bystander cells are exposed to infochemicals derived from infected cells. These vesicles have a unique lipid composition that differs from that of viruses and their infected host cells, and their cargo is composed of specific small RNAs that are predicted to target sphingolipid metabolism and cell-cycle pathways. EVs can be internalized by E. huxleyi cells, which consequently leads to a faster viral infection dynamic. EVs can also prolong EhV half-life in the extracellular milieu. We propose that EVs are exploited by viruses to sustain efficient infectivity and propagation across E. huxleyi blooms. As these algal blooms have an immense impact on the cycling of carbon and other nutrients11,12, this mode of cell–cell communication may influence the fate of the blooms and, consequently, the composition and flow of nutrients in marine microbial food webs.

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Fig. 1: EVs produced by E. huxleyi during viral infection and in response to infochemical treatment.
Fig. 2: Characterization of lipid composition and small RNA cargo of EVs produced by E. huxleyi during infection and VFL treatment.
Fig. 3: Effect of EVs on infection dynamics and viral decay rate.
Fig. 4: Proposed model to describe the effect of EVs on viral infection in the ocean.

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Acknowledgements

We thank Z. Porat from the Life Sciences Core Facilities, the Weizmann Institute of Science for assistance with ImageStream analysis, C. Bessudo from the Department of Plant and Environmental Sciences at the Weizmann Institute of Science for support with confocal microscopy and O. Yaron, currently at Bar Ilan University, for constructing the small RNA libraries. We also thank S. Graf van Creveld from the Vardi lab for the initial design of the model, I. Sher from the Design, Photography and Printing Branch at the Weizmann Institute of Science for assistance in designing the graphs for this manuscript and J. Weitz from the Georgia Institute of Technology for fruitful discussion. This research was supported by the European Research Council StG (INFOTROPHIC grant no. 280991) and CoG (VIROCELLSPHERE grant no. 681715) and by generous support from the Edith and Nathan Goldenberg Career Development Chair to A.V. The EM studies were supported in part by the Irving and Cherna Moskowitz Center for Nano and Bio-Nano Imaging at the Weizmann Institute of Science.

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D.S. and A.V. conceived and designed the experiments, D.S., S.R. and A.V. wrote the manuscript. S.G.W. conducted the cryo-TEM experiment. S.M. performed the lipodomic analysis and E.F., D.S. and S.R. analysed the small RNA data.

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Correspondence to Assaf Vardi.

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Schatz, D., Rosenwasser, S., Malitsky, S. et al. Communication via extracellular vesicles enhances viral infection of a cosmopolitan alga. Nat Microbiol 2, 1485–1492 (2017). https://doi.org/10.1038/s41564-017-0024-3

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