PONE-D-22-29062Changes in the mRNAexpression of glycolysis-related enzymes of Candida albicans during inhibition of intramitochondrial catabolism under anaerobic conditionPLOS ONE

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Reviewer #2: Yes

Reviewer #3: No

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Reviewer #2: No

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Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

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Reviewer #1: The manuscript is interesting, since it provides studies on the regulation of PFK1 as a regulator of glycolysis and possibly growth and physiology of C. albicans. As the authors propose, more studies are required, particularly the measurement of the actual activities of the different enzymes, as well as the levels of ATP under the different conditions used.

However, the experiments are a good start to go more deeply into the reagulation of metabolism, but more importanly, the infectivity of this yeast. Pehaps also, a comparative study with. S,. cerevisiae, as a model yeast. should be included in future experiments.

Reviewer #2: This study does not have any novelty, as we already knows about almost all the paradigm during anaerobic or hypoxia conditions in which cells produces frequent energy by glycolysis or HMP shunt and not through by OXPHOS mechanism in eukaryotic system. The other part of this study is to check only m-RNA expression are not only promising option to correct prediction of protein or enzyme expression, so for that authors should need to focus on proteomics and metabolomics domain for the better elucidation in anaerobic conditions in Candida Species.

Reviewer #3: Reviewer comments

Candida albicans is a major opportunistic pathogen of human capable of causing both superficial and systemic infections. Systemic C. albicans infection has emerged as a major cause of morbidity and mortality in immunocompromised patients. In the present article, the authors have studied the differential mRNA expression of enzymes in the glycolysis and alcohol fermentation to prove that C. albicans obtains energy by carbohydrate catabolism in the early phase of environmental change that helps them survive in various parts of the host. However, the claims made in the article about the pathogenesis potential of C. albicans and glycolysis require better validation.

The following are my comments

Major comments

1. The introduction and discussion should be revised and strengthened

2. Discussion: There are no experiments to prove that auto brewery syndrome is due to the ability of C. albicans to rapidly respond to environmental changes. Further it cannot be claimed by the results of comparing just two C. albicans.

3. The difference in gene expression among strains of candida in similar culture conditions needs to explained better with substantial experimental evidence.

Minor comments

1. Introduction: Line 45-46 should be rephrased

2. Introduction: Line 67-68 should be rechecked. Regulation of PFK1 was studied after partial purification of the enzyme.

3. Methods: Line 81-84. Mention the read out of the growth curve assay. Was the number of yeast cell counted using a hemocytometer or by determining the OD or CFU?

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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Attachments

Attachment

Submitted filename: Plos Comments.pdf

Changes in the mRNAexpression of glycolysis-related enzymes of Candida albicans during inhibition of intramitochondrial catabolism under anaerobic condition

PONE-D-22-29062R1

Dear Dr. Takanori Narita,

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.

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Kind regards,

Atul Vashist, PhD

Academic Editor

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Additional Editor Comments (optional):

Authors are requested to please address the one minor comment made by Reviewer 1 and accordingly incorporate this in the manuscript. 

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

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2. 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

Reviewer #3: Partly

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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6. 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: There is only one minor comment: FCCP does not exactly inhibit oxidative phosphorylation, but uncouples it

Reviewer #2: (No Response)

Reviewer #3: The revised manuscript can be accepted.

Candida albicans is a major opportunistic pathogen of human capable of causing both superficial and systemic infections. Systemic C. albicans infection has emerged as a major cause of morbidity and mortality in immunocompromised patients. In the present article, the authors have studied the differential mRNA expression of enzymes in the glycolysis and alcohol fermentation to prove that C. albicans obtains energy by carbohydrate catabolism in the early phase of environmental change that helps them survive in various parts of the host.

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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: Yes: Antonio Peña

Reviewer #2: Yes: Vivek Singh

Reviewer #3: No

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