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