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Localized production of defence chemicals by intracellular symbionts of Haliclona sponges

Abstract

Marine sponges often house small-molecule-producing symbionts extracellularly in their mesohyl, providing the host with a means of chemical defence against predation and microbial infection. Here, we report an intriguing case of chemically mediated symbiosis between the renieramycin-containing sponge Haliclona sp. and its herein discovered renieramycin-producing symbiont Candidatus Endohaliclona renieramycinifaciens. Remarkably, Ca. E. renieramycinifaciens has undergone extreme genome reduction where it has lost almost all necessary elements for free living while maintaining a complex, multi-copy plasmid-encoded biosynthetic gene cluster for renieramycin biosynthesis. In return, the sponge houses Ca. E. renieramycinifaciens in previously uncharacterized cellular reservoirs (chemobacteriocytes), where it can acquire nutrients from the host and avoid bacterial competition. This relationship is highly specific to a single clade of Haliclona sponges. Our study reveals intracellular symbionts as an understudied source for defence chemicals in the oldest-living metazoans and paves the way towards discovering similar systems in other marine sponges.

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Data availability

The data that support the findings of this study are available from the corresponding author on request. The Ca. E. renieramycinifaciens genomes have been deposited to the IMG (Joint Genome Institute, Department of Energy) public repository, under IMG submission IDs 151197, 151198, 119799 and 119800.

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Competing interests

M.S.D. is a member of the Scientific Advisory Board for Deepbiome Therapeutics and a consultant for Flagship Pioneering.

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Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Acknowledgements

We thank E. W. Schmidt, M. K. Harper-Ireland and C. Ireland at the University of Utah for providing samples Ren-PNG-07060, Ren-PNG-07113 and Ren-Pal-02, and the Republic of Palau, Papua New Guinea and the Republic of Indonesia as original sources for the sponge samples studied here. We thank M. K. Harper-Ireland and C. Ireland at the University of Utah for the underwater photograph of the Haliclona sponge shown in Fig. 1. We are grateful to C. DeCoste and the Molecular Biology Flow Cytometry Resource Facility (partially supported by the Cancer Institute of New Jersey Cancer Center Support Grant P30CA072720) for assistance with flow cytometry; P. Shao and the Molecular Biology Electron Microscopy Core Facility for assistance with TEM; G. Laevsky, the Molecular Biology Confocal Microscopy Core Facility (a Nikon Center of Excellence) and J. Zan for assistance with FISH and microscopy experiments; G. Hrebikova and A. Ploss for assistance with LCM; W. Wang and the Lewis Sigler Institute Sequencing Core Facility for assistance with high-throughput sequencing; M. Cahn for assistance with metagenomic data analysis; S. Chatterjee for general assistance; Y. Sugimoto and P. Chankhamjon for assistance with NMR and HPLC–HR-MS; and the rest of the Donia lab for useful discussions. We also thank the anonymous Nature Microbiology reviewer who suggested the name Ca. E. renieramycinifaciens for the symbiont discovered in this study. Funding for this project has been provided by Princeton University, and M.S.D. is funded by an NIH Director’s New Innovator Award (ID: 1DP2AI124441).

Author information

M.D.T.-M. and M.S.D. designed the study. M.D.T.-M., J.N.B. and M.S.D. performed the experiments, analysed the data and wrote the manuscript.

Competing interests

M.S.D. is a member of the Scientific Advisory Board for Deepbiome Therapeutics and a consultant for Flagship Pioneering.

Correspondence to Mohamed S. Donia.

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Supplementary Notes, Supplementary Tables 1–5, Supplementary Figures 1–9 and Supplementary References.

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Fig. 1: Chemistry of Haliclona sponges.
Fig. 2: Renieramycin biosynthesis.
Fig. 3: Ca. E. renieramycinifaciens genomes and plasmids.
Fig. 4: p-ren and Ca. E. renieramycinifaciens colocalize with the largest sponge particles.
Fig. 5: Localization of Ca. E. renieramycinifaciens in sponge chemobacteriocytes.
Fig. 6: Host specificity of Ca. E. renieramycinifaciens.