Bacteria regulate choanoflagellate development with lipid activators, inhibitors, and synergists
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.\n\nSignificance StatementBacterial 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.