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

Department of Pharmacology, University of Texas Southwestern Medical Center, United States
Department of Biochemistry, University of Texas Southwestern Medical Center, United States
Department of Biology, Millersville University of Pennsylvania, United States
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, United States
Department of Molecular Biology, University of Texas Southwestern Medical Center, United States
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, United States

Dec 7, 2021

https://doi.org/10.7554/eLife.73535

Open access
Copyright information

Decision letter
Author response

Decision letter

Phillip A Newmark

Reviewing Editor; Morgridge Institute for Research, United States
Dominique Soldati-Favre

Senior Editor; University of Geneva, Switzerland
Mostafa Zamanian

Reviewer; University of Wisconsin, United States
Keith Yamamoto

Reviewer

Our editorial process produces two outputs: (i) public reviews designed to be posted alongside the preprint for the benefit of readers; (ii) feedback on the manuscript for the authors, including requests for revisions, shown below. We also include an acceptance summary that explains what the editors found interesting or important about the work.

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).

https://doi.org/10.7554/eLife.73535.sa1

Author response

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.

https://doi.org/10.7554/eLife.73535.sa2