https://orcid.org/0000-0001-6492-2707
Peer Review History
| Original SubmissionJune 10, 2021 |
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Dear Professor O'Riordan, Thank you very much for submitting your manuscript "Comparative transcriptional profiling of the early host response to infection by typhoidal and non-typhoidal Salmonella serovars in human intestinal organoids" for consideration at PLOS Pathogens. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers, please accept our apologies for the exceptionally long process in this instance. The reviewers appreciated the attention to an important topic. Based on the reviews, we are likely to accept this manuscript for publication, providing that you modify the text of the manuscript according to the review recommendations. Please prepare and submit your revised manuscript within 30 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email. When you are ready to resubmit, please upload the following: [1] A letter containing a detailed list of your responses to all review comments, and a description of the changes you have made in the manuscript. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out [2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file). Important additional instructions are given below your reviewer comments. Thank you again for your submission to our journal. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments. Sincerely, Sophie Helaine Associate Editor PLOS Pathogens Nina Salama Section Editor PLOS Pathogens Kasturi Haldar Editor-in-Chief PLOS Pathogens orcid.org/0000-0001-5065-158X Michael Malim Editor-in-Chief PLOS Pathogens *********************** Reviewer Comments (if any, and for reference): Reviewer's Responses to Questions Part I - Summary Please use this section to discuss strengths/weaknesses of study, novelty/significance, general execution and scholarship. Reviewer #1: In the revised version of this study, Abuaita and colleagues have successfully addressed a majority of the comments and have provided sound experimental evidence to validate the transcriptome analysis. While the manuscript remains largely descriptive, it now offers a solid and informative experimental base for a variety of interesting follow-up studies. Especially the newly added data on SPI1- and SPI2-expression by the different strains, as well as the comparison of expression signatures in different models and studies adds very interesting new insights and further validates HIOs as a model for studying host-microbe interaction. A few points however remain to be resolved. Reviewer #2: Abuaita et al. provide an extensive transcriptomic characterization of a human intestinal organoids exposed to three Salmonella serovars (Typhimurium (STM), Enteritidis (SE) and Typhi (ST)). The originality of the paper lies on the use of the organoids that best mimic the in vivo conditions. I commend this paper because it constitutes an important resource for the field. The revision has clarified my concerns. ********** Part II – Major Issues: Key Experiments Required for Acceptance Please use this section to detail the key new experiments or modifications of existing experiments that should be absolutely required to validate study conclusions. Generally, there should be no more than 3 such required experiments or major modifications for a "Major Revision" recommendation. If more than 3 experiments are necessary to validate the study conclusions, then you are encouraged to recommend "Reject". Reviewer #1: - The authors have added some clarification regarding the inoculum sizes used, but it remains unclear which inoculum size was used for the 2.5h time point. It seems that in Fig. 1, 10^3 CFU were injected (according to l. 124-125), while for the transcriptome data set it sounds like the incoculum size for the 2.5h time point was 10^5 CFU (l. 173-175). Unfortunately, nothing is stated in the methods section regarding this time point. This point needs to be clarified, especially as the low inoculum seems to result in differences in Salmonella loads for the different strains tested, while there is no evident difference with the higher inoculum at 8 hpi. If the 2.5h infection for the transcriptome data set was indeed performed with a different inoculum size than the data presented in Fig. 1B, it would be highly important for the interpretability of the data set to add the CFU data also for this time point and inoculum size. Stating the respective inoculum sizes for the different experiments in the figure legends (Fig. 1 and 2) would make it much easier for the reader to understand the experimental setup. - While it is evident that the authors cannot test numerous strains per serovar and it is reasonable to choose the best-characterized ones for the experimental setup used here, the substantial differences between strains of one serovar should anyhow be discussed to make clear to the reader that host responses likely vary substantially even between strains of one serovar. It should bepointed out that the response of one strain cannot be generalized to the entire serovar. Reviewer #2: However, I still have a strong concern on the massive experimental variability between the three serovars that the authors outline in Figure 1 (Figure 1B and 1C). This variability is clearly bounded to the experimental set-up and I believe that further studies will refine this problem. Furthermore, in the current setting, the authors cannot discriminate the host response induced solely by the extracellular versus the intracellular bacteria. The discussion should clearly outline that the heterogeneity in the host response can be due to these confounding factors. ********** Part III – Minor Issues: Editorial and Data Presentation Modifications Please use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. Reviewer #1: - Please plot individual data points instead/in addition for Fig 5D, S3 - L. 103: "…to compare the transcriptomes of intestinal…" - L. 174: please clarify what you mean with "similar" (similar to which condition?) - L. 213: add "at 8 hpi" to clarify - L. 319: "..during these infections were not sufficient…" - L. 456-457 "…other serovars exhibit different infection patterns in different organisms": please provide references - L. 487: "…despite inducing their…" Reviewer #2: No Minor Issues ********** PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No Figure Files: While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Data Requirements: Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5. Reproducibility: To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols References: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. |
| Revision 1 |
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Dear Prof O'Riordan, We are pleased to inform you that your manuscript 'Comparative transcriptional profiling of the early host response to infection by typhoidal and non-typhoidal Salmonella serovars in human intestinal organoids' has been provisionally accepted for publication in PLOS Pathogens. Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests. Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated. IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript. Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS. Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Pathogens. Best regards, Sophie Helaine Associate Editor PLOS Pathogens Nina Salama Section Editor PLOS Pathogens Kasturi Haldar Editor-in-Chief PLOS Pathogens orcid.org/0000-0001-5065-158X Michael Malim Editor-in-Chief PLOS Pathogens *********************************************************** Reviewer Comments (if any, and for reference): |
| Formally Accepted |
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Dear Prof. O'Riordan, We are delighted to inform you that your manuscript, "Comparative transcriptional profiling of the early host response to infection by typhoidal and non-typhoidal Salmonella serovars in human intestinal organoids," has been formally accepted for publication in PLOS Pathogens. We have now passed your article onto the PLOS Production Department who will complete the rest of the pre-publication process. All authors will receive a confirmation email upon publication. The corresponding author will soon be receiving a typeset proof for review, to ensure errors have not been introduced during production. Please review the PDF proof of your manuscript carefully, as this is the last chance to correct any scientific or type-setting errors. Please note that major changes, or those which affect the scientific understanding of the work, will likely cause delays to the publication date of your manuscript. Note: Proofs for Front Matter articles (Pearls, Reviews, Opinions, etc...) are generated on a different schedule and may not be made available as quickly. Soon after your final files are uploaded, the early version of your manuscript, if you opted to have an early version of your article, will be published online. The date of the early version will be your article's publication date. The final article will be published to the same URL, and all versions of the paper will be accessible to readers. Thank you again for supporting open-access publishing; we are looking forward to publishing your work in PLOS Pathogens. Best regards, Kasturi Haldar Editor-in-Chief PLOS Pathogens orcid.org/0000-0001-5065-158X Michael Malim Editor-in-Chief PLOS Pathogens |
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