Bacterial lipids activate, synergize, and inhibit a developmental switch in choanoflagellates

Edited by Benjamin F. Cravatt, The Scripps Research Institute, La Jolla, CA, and approved May 19, 2016 (received for review March 25, 2016)
June 27, 2016
113 (28) 7894-7899

Significance

Bacterial symbionts profoundly influence the biology of their animal hosts, yet complex interactions between animals and their resident bacteria often make it challenging to characterize the molecules and mechanisms. Simple model systems can reveal fundamental processes underlying interactions between eukaryotes and their associated microbial communities and provide insight into how bacteria regulate animal biology. In this study we isolate and characterize bacterial molecules that regulate multicellular development in the closest living relatives of animals, the choanoflagellate. We find that multiple bacterially derived lipids converge to activate, enhance, and inhibit choanoflagellate multicellular development.

Abstract

In choanoflagellates, the closest living relatives of animals, multicellular rosette development is regulated by environmental bacteria. The simplicity of this evolutionarily relevant interaction provides an opportunity to identify the molecules and regulatory logic underpinning bacterial regulation of development. We find that the rosette-inducing bacterium Algoriphagus machipongonensis produces three structurally divergent classes of bioactive lipids that, together, activate, enhance, and inhibit rosette development in the choanoflagellate Salpingoeca rosetta. One class of molecules, the lysophosphatidylethanolamines (LPEs), elicits no response on its own but synergizes with activating sulfonolipid rosette-inducing factors (RIFs) to recapitulate the full bioactivity of live Algoriphagus. LPEs, although ubiquitous in bacteria and eukaryotes, have not previously been implicated in the regulation of a host–microbe interaction. This study reveals that multiple bacterially produced lipids converge to activate, enhance, and inhibit multicellular development in a choanoflagellate.

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Acknowledgments

We thank M. Abedin, D. Booth, B. Davidson, and J. Rawls for critical reading of the manuscript; R. Alegado for early discussions; L. Wetzel for help with “violin” plots; and J. Wang at the Harvard Small Molecule Mass Spec Facility for help with high-resolution mass spectrometry. N.K. is a senior fellow in the Integrated Microbial Biodiversity Program of the Canadian Institute for Advanced Research.

Supporting Information

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Supporting Information

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Information & Authors

Information

Published in

Go to Proceedings of the National Academy of Sciences
Go to Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
Vol. 113 | No. 28
July 12, 2016
PubMed: 27354530

Classifications

Submission history

Published online: June 27, 2016
Published in issue: July 12, 2016

Keywords

  1. choanoflagellates
  2. bacteria
  3. host–microbe
  4. sulfonolipid
  5. multicellularity

Acknowledgments

We thank M. Abedin, D. Booth, B. Davidson, and J. Rawls for critical reading of the manuscript; R. Alegado for early discussions; L. Wetzel for help with “violin” plots; and J. Wang at the Harvard Small Molecule Mass Spec Facility for help with high-resolution mass spectrometry. N.K. is a senior fellow in the Integrated Microbial Biodiversity Program of the Canadian Institute for Advanced Research.

Notes

This article is a PNAS Direct Submission.

Authors

Affiliations

Arielle Woznica1
Howard Hughes Medical Institute, University of California, Berkeley, CA 94720;
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720;
Alexandra M. Cantley1
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115;
Christine Beemelmanns
Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll Institute, 07745 Jena, Germany;
Elizaveta Freinkman
Whitehead Institute for Biomedical Research, Cambridge, MA 02142
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115;
Howard Hughes Medical Institute, University of California, Berkeley, CA 94720;
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720;

Notes

2
To whom correspondence may be addressed. Email: [email protected] or [email protected].
Author contributions: A.W., A.M.C., J.C., and N.K. designed research; A.W., A.M.C., C.B., and E.F. performed research; A.W., A.M.C., C.B., J.C., and N.K. analyzed data; and A.W., A.M.C., J.C., and N.K. wrote the paper.
1
A.W. and A.M.C. contributed equally to this work.

Competing Interests

The authors declare no conflict of interest.

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    Bacterial lipids activate, synergize, and inhibit a developmental switch in choanoflagellates
    Proceedings of the National Academy of Sciences
    • Vol. 113
    • No. 28
    • pp. 7679-E4118

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