Role of the JAK2/STAT3 pathway on infection of Francisella novicida

Sonoko Matsumoto; Takashi Shimizu; Akihiko Uda; Kenta Watanabe; Masahisa Watarai

doi:10.1371/journal.pone.0310120

Peer Review History

Original SubmissionJuly 7, 2024
19 Aug 2024 Decision Letter - Ebrahim Shokoohi, Editor PONE-D-24-27526Effect of the JAK2/STAT3 Pathway on Internalization of Francisella novicida.PLOS ONE Dear Dr. Shimizu, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Oct 03 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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Currently, your Funding Statement reads as follows: "SM: JST SPRING Grant Number JPMJSP2111 TS: JSPS KAKENHI Grant Number 22K07054, MW: JSPS KAKENHI Grant Number 21H02360". Please include your amended statements within your cover letter; we will change the online submission form on your behalf. 6. 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 If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references.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 If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. Additional Editor Comments: Dear Authors We have received the feedback for your work. You need to address the concerns of the Referees. The comments are given for you reference. Please note that I have acted as a reviewer for this manuscript, and you will find my comments below, under Reviewer 1. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? 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Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The paper entitled Effect of the JAK2/STAT3 Pathway on Internalization of Francisella novicida; is very interning. It was written well and provided with sufficient data. However, some concern need to be addressed. 1-Why the authors choose Cucurbitacin I? What about the other inhibitors? 2-What is the source of Cucurbitacin I? 3-What is the purpose of providing merge, DIC ,and GFP? 4-Interfiering of the JAK2/STAT3 Pathway by Cucurbitacin, how it affect the phenotype of the bacteria? 5-The title of the paper is not in line with the context. It should be revised by the authors. Internalization, and withing the text is all about inhibiting the pathway by Cucurbitacin I. Reviewer #2: The paper was checked as Effect of the JAK2/STAT3 Pathway on Internalization of Francisella novicida It is an exciting paper on the plant extract main ingredient effect on the bacteria, which bring valuable insight into the bacterial physiology and biology within the cells. However, the authors must explain how they choose Cucurbitacin I, and what was the rate of inhibition? The title of the paper also confusing as only bacteria and the pathway included, but not the effect of plant extract on the pathway. Overall, the manuscript is well written, and I would recommend to be published in PLoS One after a minor revision. ****** 6. 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 ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment 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. Registration is free. 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 PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0310120.r001
Revision 1
21 Aug 2024 Author Response Thank you for reviewing our paper entitled '' Effect of the JAK2/STAT3 Pathway on Internalization of Francisella novicida'' by Matsumoto et al. (PONE-D-24-27526), and giving us an opportunity to submit our manuscript again. We corrected our manuscript according to comments of the editor and reviewers. We believe that the revised manuscript is improved significantly with the referees’ advice and now acceptable for publication in PLOS One. 1. When submitting your revision, we need you to address these additional requirements. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf --As you suggested, we checked the requirements and made small changes, e.g. to font sizes. 2. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed: https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.1027424/full In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed. -- As you suggest, we checked our manuscript using iThenticate software and rephrase some sentences (Line 20-21, 91-92, 161-162). 3. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. -- As you suggest, we arranged the ‘Funding Information’. 4. Thank you for stating the following financial disclosure: "SM: JST SPRING Grant Number JPMJSP2111 TS: JSPS KAKENHI Grant Number 22K07054, MW: JSPS KAKENHI Grant Number 21H02360". Please state what role the funders took in the study. If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." If this statement is not correct you must amend it as needed. Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf. --As you suggested, we added the sentence in cover letter. 5. Thank you for stating the following in the Acknowledgments Section of your manuscript: "This work was supported by JST SPRING Grant Number JPMJSP2111, JSPS KAKENHI Grant Number 22K07054, JSPS KAKENHI Grant Number 21H02360, and Molecular Profiling Committee, Grant-in-Aid for Transformative Research Areas “Advanced Animal Model Support (AdAMS)” from JSPS KAKENHI Grant Number JP 22H04922." We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: "SM: JST SPRING Grant Number JPMJSP2111 TS: JSPS KAKENHI Grant Number 22K07054, MW: JSPS KAKENHI Grant Number 21H02360". Please include your amended statements within your cover letter; we will change the online submission form on your behalf. --Thank you for checking our funding information. We removed Acknowledge section from the manuscript. The information listed above is correct. We added explanation about this information in cover letter. 6. 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. --We checked references and found no problems. Reviewers' comments: Reviewer's Responses to Questions Comments to the Author Reviewer #1: The paper entitled Effect of the JAK2/STAT3 Pathway on Internalization of Francisella novicida; is very interning. It was written well and provided with sufficient data. However, some concern need to be addressed. --Thank you for your reviewing. As you suggested we corrected our manuscript. 1- Why the authors choose Cucurbitacin I? What about the other inhibitors? --In this study, we identified 56 inhibitors that negatively regulate F. novicida infection. Among them 3 inhibitors were related to Jak-2/STAT3 pathway. Therefore we thought that Jak-2/STAT3 pathway might be involved in F. novicida infection. Cucurbitacin was used as a representative inhibitor of the Jak-2/Stat3 pathway. Additionally, other promising inhibitors have been identified, including those targeting mTOR and p53, which are currently undergoing analysis. To explain this we rewrote sentences (line 197-201). 2- What is the source of Cucurbitacin I? --Cucurbitacin I is a natural cell-permeable triterpenoid isolated from Cucurbitaceae, and is a selective inhibitor of JAK2/STAT3. The Cucurbitacin I is explained in Discussion section (line334-335). 3- What is the purpose of providing merge, DIC ,and GFP? --DIC was used to show the location of the cells; the intention was to show that the bacteria were intracellularly located by using merged images with the DIC. 4- Interfiering of the JAK2/STAT3 Pathway by Cucurbitacin, how it affect the phenotype of the bacteria? --We thought cucurbitacin might have an antibiotic effect, so we added cucurbitacin to the medium and investigated growth, but found that cucurbitacin had no effect on bacterial growth (Fig 2). From these data we consider that cucurbitacin does not affect the phenotype of F. novicida. 5- The title of the paper is not in line with the context. It should be revised by the authors. Internalization, and withing the text is all about inhibiting the pathway by Cucurbitacin I. --We changed the title as you suggested (line 1). Reviewer #2: The paper was checked as Effect of the JAK2/STAT3 Pathway on Internalization of Francisella novicida. It is an exciting paper on the plant extract main ingredient effect on the bacteria, which bring valuable insight into the bacterial physiology and biology within the cells. --Thank you for your review. We corrected our manuscript as you suggested. However, the authors must explain how they choose Cucurbitacin I, and what was the rate of inhibition? --In this study, we identified 56 inhibitors that negatively regulate F. novicida infection. Among them 3 inhibitors were related to Jak-2/STAT3 pathway. Therefore we thought that Jak-2/STAT3 pathway might be involved in F. novicida infection. Cucurbitacin was used as a representative inhibitor of the Jak-2/Stat3 pathway. Additionally, other promising inhibitors have been identified, including those targeting mTOR and p53, which are currently undergoing analysis. To explain this we rewrote sentences (line 197-201). In the first screening we used the intensity of GFP, so the rate of inhibition could only be expressed as a relative value compared to the control (table S1). Therefor, we measured the effect of Cucurbitacin I on F. novicida infection in Fig. 1. The title of the paper also confusing as only bacteria and the pathway included, but not the effect of plant extract on the pathway. --We changed the title as you suggest(line 1). Overall, the manuscript is well written, and I would recommend to be published in PLoS One after a minor revision. 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. Registration is free. 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 PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. --We checked figures with PACE and converted tiff files were uploaded to the journal online system. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0310120.r002
26 Aug 2024 Decision Letter - Ebrahim Shokoohi, Editor Role of the JAK2/STAT3 Pathway on Infection of Francisella novicida. PONE-D-24-27526R1 Dear Dr.Takashi Shimizu, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Ebrahim Shokoohi Academic Editor PLOS ONE Additional Editor Comments (optional): Authors improved the paper and answered all raised concerns by the Referees. Reviewers' comments: no comments https://doi.org/10.1371/journal.pone.0310120.r003
Formally Accepted
30 Aug 2024 Acceptance Letter - Ebrahim Shokoohi, Editor PONE-D-24-27526R1 PLOS ONE Dear Dr. Shimizu, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Ebrahim Shokoohi Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0310120.r004

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