Investigation of the Relation between Temperature and M13 Phage Production via ATP Expenditure
Round 1
Reviewer 1 Report
The article entitled "Effect of Temperature on M13 Bacteriophage Production in Liter-Scale Bioreactor" presents the effect of temperature on the production of M13 phages and corelate it with the ATP expenditure at 3 different temperatures (25 ℃, 30 ℃, and 37 ℃).
Overall the article lacks novelty as the work has been already reported by Warner et al. (Warner et al.,2014), which is not even cited in this article?
Warner CM, Barker N, Lee SW, Perkins EJ. M13 bacteriophage production for large-scale applications. Bioprocess Biosyst Eng. 2014 Oct;37(10):2067-72. doi: 10.1007/s00449-014-1184-7. Epub 2014 Apr 13. PMID: 24728964. https://link.springer.com/article/10.1007/s00449-014-1184-7
The article seems to be limited to just 3 temperature ranges and other variables like media, pH, or even host and phage concentrations are not even considered for the experiments. Which makes the article too much superficial ! Just by considering 3 temperatures and ATP expenditures will not provide actual factors for M13 phage production optimization. The article lacks the rationale for the presented work which makes the reported study further weak.
Also, self citation of the corresponding author is detected (5 times) in the whole text, which do not have any direct co-relation!
For the article to be considered for publication extensive literature review must be done in order to support the conducted experiments as well as to explain why the above mentioned factors were not considered for the work which are either commonly predictable and feasible rather then technically limiting.
Author Response
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Author Response File: Author Response.pdf
Reviewer 2 Report
Authors conduct a research about effect of temperature on M13 bacteriophage production in Li-ter-Scale bioreactor.
The paper lacks originality, the study is ordinary and the content is not abundant.
Many formulas lack sources, it is not original.
The literature review is not enough and is presented not so good.
As a whole, the research level of this manuscript is simple and unsuitable for a publication.
Maybe, it can be improved a lot after a major revision.
Author Response
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Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
The revised article with the modified title "Investigation of the Relation between Temperature and M13 Phage Production via ATP expenditure" appropriately explains the work presented in this article. Considering the proper representation of the findings and explanations of the results thereof can be of importance for the phage research community for phage yield optimization in terms of ATP expenditure during different temperature conditions. Now the title clearly justifies the work performed and the results presented!
I would like to suggest the authors to further explain the other parameters (through citing other references) which support their results to further validate these findings as it will help both the research community as well as those involved in the commercial production of phages.
Here are some of the articles which I suggest the authors consider for comparing their results in results and discussions are as follows:
Mahmoudabadi, G., Milo, R., & Phillips, R. (2017). Energetic cost of building a virus. Proceedings of the National Academy of Sciences of the United States of America, 114(22), E4324–E4333. https://doi.org/10.1073/pnas.1701670114
Serwer, P., & Wright, E. T. (2017). ATP-Driven Contraction of Phage T3 Capsids with DNA Incompletely Packaged In Vivo. Viruses, 9(5), 119. https://doi.org/10.3390/v9050119
Warner, C. M., Barker, N., Lee, S. W., & Perkins, E. J. (2014). M13 bacteriophage production for large-scale applications. Bioprocess and biosystems engineering, 37(10), 2067–2072. https://doi.org/10.1007/s00449-014-1184-7
Rücker, B., Almeida, M. E., Libermann, T. A., Zerbini, L. F., Wink, M. R., & Sarkis, J. J. (2008). E-NTPDases and ecto-5'-nucleotidase expression profile in rat heart left ventricle and the extracellular nucleotide hydrolysis by their nerve terminal endings. Life sciences, 82(9-10), 477–486. https://doi.org/10.1016/j.lfs.2007.12.003
The critical points to stress are related to the variation of ATP expenditure associated with the type of media composition (and/or composition of media used), the host bacteria and phage involved, and the physicochemical properties affecting these results (including pH, etc.). These factors are important to discuss because the ionic concentrations of different media components vary depending on the different physicochemical parameters. Some articles suggest that the optimum pH for maximum ATP hydrolysis is around pH 8.0 (which is close to the one used here pH 7.4). Hence, it makes the discussion of the results obtained from the conditions used for performing the experiments more important rather than just focusing on one parameter i.e. temperature to take all the credit for the ATP expenditure!
Apart from this the article provides new findings for phage M13 production optimization based on temperature and ATP expenditure and can be of considerable importance for phage research in general and for M13 yield enhancement in particular.
Author Response
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Author Response File: Author Response.pdf
Reviewer 2 Report
Although the author has made extensive revisions to the first draft, the following suggestions are still required for major revisions:
1. The process of many outcomes is not clear.
2. Many of the required parameter values are not presented.
3. No field experiments.
4. The innovation and necessity of this research need to be further emphasized in the introduction.
5. This paper studies the production of biochemical related works. In order to improve the scope of research, the introduction can also learn and cite the research carried out in mechanical manufacturing to improve product production accuracy. Such as "Research on vibration model and vibration performance of cold orbital forging machines [J]. Proceedings of the Institution of Mechanical Engineers, Part B: Journal of Engineering Manufacture, 2022, 236 (6-7): 828-843."
6. Some references are not in MDPI format.
Author Response
Please see the attachment.
Author Response File: Author Response.pdf