Characterization of the endogenous DAF-12 ligand and its use as an anthelmintic agent in Strongyloides stercoralis

Decision letter after peer review:

Thank you for submitting your article "Characterization of the Endogenous DAF-12 Ligand and Its Use as an Anthelmintic Agent in Strongyloides stercoralis" for consideration by eLife. Your article has been reviewed by 2 peer reviewers, and the evaluation has been overseen by Phillip Newmark as Reviewing Editor and Dominique Soldati-Favre as the Senior Editor. The following individuals involved in review of your submission have agreed to reveal their identity: Mostafa Zamanian (Reviewer #1); Keith Yamamoto (Reviewer #2).

The reviewers have discussed their reviews with one another, and the Reviewing Editor has drafted this to help you prepare a revised submission.

Essential revisions:

1) As noted by reviewer #2 (see their public review), the Results section claims that unliganded Ss-DAF-12 is required for production of infectious L3i larvae, but this is not demonstrated here. The authors could either provide evidence demonstrating the requirement of unliganded Ss-DAF-12 for L3i production, or they could summarize briefly in the Results section how they established this requirement, citing their PNAS 2021 publication at that point (as well as in the Discussion, where it is currently first cited in this context).

Essential revisions:

1) As noted by reviewer #2 (see their public review), the Results section claims that unliganded Ss-DAF-12 is required for production of infectious L3i larvae, but this is not demonstrated here. The authors could either provide evidence demonstrating the requirement of unliganded Ss-DAF-12 for L3i production, or they could summarize briefly in the Results section how they established this requirement, citing their PNAS 2021 publication at that point (as well as in the Discussion, where it is currently first cited in this context).

We appreciate the reviewer’s comment and to address this we have updated the text to state in the Introduction (lines 98-100) and Results (lines 166-167) that the findings highlighted in our previous PNAS paper did demonstrate that Ss-DAF-12 is required for L3i production. This was also already stated in the first paragraph of the Discussion (lines 342-343). In addition, we note that the present study also demonstrates this requirement by showing that the absence of the DAF-12 ligand (and thus unliganded Ss-DAF-12) is necessary for L3i formation and the presence of the ligand is necessary and sufficient for reactivation of L3i arrest and reproductive development.