A bacterial sulfonolipid triggers multicellular development in the closest living relatives of animals

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This paper reports that a bacterial sulfonolipid is able to induce colony development in a choanoflagellate. The active compound, which is produced by the bacterium in tiny amounts, turns out to be active in femtomolar concentrations. Its structure (but not its stereochemistry) is determined on the basis of extensive mass spectrometric and NMR analysis. This is a beautiful piece of work, demonstrating that this sulfonolipid produced by bacteria upon which the choanoflagellate feeds has a profound influence on the predator's development.

Specifically, a particular choanoflagellate species will form rosettes, i.e., become multicellular, when certain species of Bacteroidetes are present. The researchers went on to purify and characterize the bacterial molecule responsible for this behavior in the protist.

The findings should be of broad interest to the community of biologists, as it includes elements of microbiology, signaling between bacterial and eukaryotic cells that is based on molecules not before known to carry out this function, and the evolution of multicellularity in the sister group to the animals, the choanoflagellates. The work represents a major contribution to concepts about the mechanisms that may have been in play when the evolutionary step to multicellularity took place ∼ a billion years ago.

The paper has implications regarding the development of eukaryotic multicellularity. The signal, a bacterial sulfonolipid, is active at remarkably low concentrations.

Each of the reviewers has a few points that you should easily be able to attend to. None of these seem to be obstacles to publication. We are particularly interested in further comment on the sensitivity of the response to sulfonolipids and the fact that pure material elicits a poor response in comparison to bacterial preparations. A comment in the discussion about where the work heads from here would also be welcome.

The fmolar activity of the signal seems extraordinary. Could the authors comment in the manuscript how this compares to other ultrasensitive receptors. Are there any described receptors that are more sensitive?

The potency of the pure compound compared to the crude extracts is low. This received comment in the manuscript. The authors conclude that it is how the signal is delivered-as a pure relatively hydrophobic compound vs in the context of the bacterial membrane. This is one possibility. It could also be that there is a second signal required for full potency- one that is inactive in the absence of sulfonolipid. We don't know yet about the receptors. Did the authors try any kind of reconstitution experiments that might speak to the hypothesis that potency of sulfonolipids is dependent on the context of delivery?

One shortcoming in this work, from an organic chemist's point of view, is that the three-dimensional structure of the signalling molecule has not been defined. With four asymmetric centers in the structure, that means that the active molecule is one of sixteen stereochemical possibilities. So, there is more to be done, and if this research group does not do it quickly, some other organic chemical research group will certainly do it for them!