A Barrier to Entry: Examining the Bacterial Outer Membrane and Antibiotic Resistance
Round 1
Reviewer 1 Report
The manuscript "Crossroads to Diffusion Barrier of Bacterial Outer Membrane and Antibiotic Resistance" is a comprehensive review of recent literature building upon review by the same author in 2017 and 2018.
The presentation and organisation of the material is of a high quality, the only error detected was that reference # 19 is missing the details of the citation. The compilations and summary of data provided in tabular form is extensive and should prove to be a useful resource.
The only aspect that is not completely clear to me is the title. I am uncertain what the author means using the term "Crossroads". The review article discusses diffusion across membranes, the implications of this for antibiotic resistance and measured resistance for a large number of systems. There does not seem to be an assessment of 'crossing' from one mechanism or approach to another. I think that the title could be modified but otherwise could be published as is.
Author Response
Dear Reviewer,
Thank you for reviewing the manuscript "Crossroads to Diffusion Barrier of Bacterial Outer Membrane and Antibiotic Resistance." I appreciate your insightful comments and suggestions, which have helped to improve the manuscript.
Based on your feedback, I have made the revisions to the manuscript. These changes have significantly strengthened the manuscript and addressed your concerns.
Once again, thank you for your thoughtful review and feedback. The revised manuscript now meets the journal's standards, and I look forward to hearing back from you.
Sincerely,
Ishan Ghai
Comments
1. The manuscript "Crossroads to Diffusion Barrier of Bacterial Outer Membrane and Antibiotic Resistance" is a comprehensive review of recent literature building upon review by the same author in 2017 and 2018. The presentation and organisation of the material is of a high quality, the only error detected was that reference # 19 is missing the details of the citation. The compilations and summary of data provided in tabular form is extensive and should prove to be a useful resource.
Response
· reference # 19 and the manuscript have been updated accordingly.
2. The only aspect that is not completely clear to me is the title. I am uncertain what the author means using the term "Crossroads". The review article discusses diffusion across membranes, the implications of this for antibiotic resistance and measured resistance for a large number of systems. There does not seem to be an assessment of 'crossing' from one mechanism or approach to another. I think that the title could be modified but otherwise could be published as is.
Response
· The title has been modified, and the new title is as follows.
"Barrier to Entry: Examining the Bacterial Outer Membrane and Antibiotic Resistance"
Reviewer 2 Report
This paper entitled "Crossroads to Diffusion Barrier of Bacterial Outer Membrane and Antibiotic Resistance" reviews the state of the art on Gram negative bacterial permeability proteins, together with an extensive list and summary of scientific work to date on the involvement of proteins and transport systems in antibiotic transport across the Gram negative bacterial cell envelope of different species. It also briefly describes some methodologies that can be used to measure the transport of antibiotics across the membrane, through each pore type, individually.
The work reveals an effort at systematisation that is commendable and which I think could be very useful for consultation.
Regarding the structure of the article, I think that the discussion chapter and the concluding remarks section could be merged or, alternatively, the concluding remarks section should be reduced to make it more succinct.
I would like to leave some suggestions for the author to improve the manuscript.
On page 1, lines 32-36, Introduction section, please change all the scientific names tio italics.
On line 41 of the same section you present the abbreviation AMR, which requires a full description
On page 2, line 49, you refer to "Gram negative antibiotics", while I believe that you mean "antibiotics that are tageted to Gram negative bacteria", instead.
On lines 52-54, again, please change all the scientific names tio italics.
The first paragraph of the section "1.1. Gram-negative bacteria and membrane proteins, line 56, I would delete "do not need any intruduction, it has". On line 59, I would put "see in figure 1B" between parentisis, as well as the last setence ""see Table 01 for different membrane proteins studied across different research experimental studies".
On page 3, line 118, you have written twice in the same sentence "ouiter membrane". I suggest that you change to: "The main aim of this review is to continue the authors' previous work 23,43 to analyse and summarise advances in understanding the role of various Gram-negative bacteria outer membrane proteins for solute/antibiotic influxs".
I also thing that maybe you should consider moving the entire paragraph (lines 116-130) to another location.
The legend of Table 1 I thing that you should replace the word "bug" by the word "bacteria" or "microorganism".
On page 7 I think that the legend of figure 1 is not very descriptive, and therefore should be improved. Additionaly the figure does not evidence any different between the transport systems shown (1 to 4).
In the section "1.2. Computing influx", on line145, I suggest that you dlete the word "lethal", or else explain what a lethal target mean.
The sentence of the first paragraf of page 8, lines 166-1767 needs to be rephrased. There is also a small typo on line 181. Instead of a comma, use a full stop, and on line 194, use a capital letter "Molecular Simulations".
On page 9, The legend of figure 2 needs to be rewritten as it does not explain the figure and is confusing.
Concerning the legend of Table 2, please don't use a capital çetter in the word "Research" om line 219, and delete the word "rigourously" on line 220.
Once again avoid the word "bug" in the table, convey with the rules for the scientific names, for example, not "E. Coli" but "E. coli", and in italics everywhere. On 13th line I believe that you should delete the word "Stu".
Please make all the above mentioned corrections into the scientific names on Table 3, too.
In the discussion section, page 20,line 234, you should correct the scientific names.
On line 238 change the word "im-permeability" to "impermeability".
On line240 I would begin the sentence like this: "Furthermore, it has (...)".
The section "2.1. Conclusive remarks" should be renamed "Concluding remarks", and, as I said before, it should be shortened.
Author Response
Dear Reviewer,
Thank you for taking the time to review our manuscript titled "Crossroads to Diffusion Barrier of Bacterial Outer Membrane and Antibiotic Resistance." I appreciate your insightful comments and suggestions, which have helped to improve the manuscript.
Based on your feedback, I have made the revisions to the manuscript. These changes have significantly strengthened the manuscript and addressed your concerns.
Once again, I would like to thank you for your thoughtful review and feedback. I hope the revised manuscript now meets the journal's standards, and I look forward to hearing back from you.
Sincerely,
Ishan Ghai
This paper entitled "Crossroads to Diffusion Barrier of Bacterial Outer Membrane and Antibiotic Resistance" reviews the state of the art on Gram negative bacterial permeability proteins, together with an extensive list and summary of scientific work to date on the involvement of proteins and transport systems in antibiotic transport across the Gram-negative bacterial cell envelope of different species. It also briefly describes some methodologies that can be used to measure the transport of antibiotics across the membrane, through each pore type, individually.
The work reveals an effort at systematisation that is commendable and which I think could be very useful for consultation.
Regarding the structure of the article, I think that the discussion chapter and the concluding remarks section could be merged or, alternatively, the concluding remarks section should be reduced to make it more succinct.
I would like to leave some suggestions for the author to improve the manuscript.
- On page 1, lines 32-36, Introduction section, please change all the scientific names to italics.
- Implemented/Corrected
- On line 41 of the same section you present the abbreviation AMR, which requires a full description
- Implemented/Corrected
- On page 2, line 49, you refer to "Gram negative antibiotics", while I believe that you mean "antibiotics that are tageted to Gram negative bacteria", instead.
- Implemented/Corrected
- On lines 52-54, again, please change all the scientific names tio italics.
- Implemented/Corrected
- The first paragraph of the section "1.1. Gram-negative bacteria and membrane proteins, line 56, I would delete "do not need any intruduction, it has". On line 59, I would put "see in figure 1B" between parentisis, as well as the last setence ""see Table 01 for different membrane proteins studied across different research experimental studies".
- Implemented/Corrected
- On page 3, line 118, you have written twice in the same sentence "ouiter membrane". I suggest that you change to: "The main aim of this review is to continue the authors' previous work 23,43 to analyse and summarise advances in understanding the role of various Gram-negative bacteria outer membrane proteins for solute/antibiotic influxs".
- Implemented/Corrected
- I also thing that maybe you should consider moving the entire paragraph (lines 116-130) to another location.
- I believe This paragraph serves the purpose very well here
- The legend of Table 1 I thing that you should replace the word "bug" by the word "bacteria" or "microorganism".
- Implemented/Corrected
- On page 7 I think that the legend of figure 1 is not very descriptive, and therefore should be improved. Additionaly the figure does not evidence any different between the transport systems shown (1 to 4).
- Figure 1 corresponds to An overview of Antibiotic resistance. and Several systems pertaining to antibiotic/antimicrobial resistance utilized by Gram-negative bacteria an overview (Structural interpretation) and antibiotic/antimicrobial resistance mechanism correlated with Outer membrane proteins (Omps) modification.
- The figure serves the purpose very well here.
- In the section "1.2. Computing influx", on line145, I suggest that you dlete the word "lethal", or else explain what a lethal target mean.
- Removed
- The sentence of the first paragraf of page 8, lines 166-1767 needs to be rephrased. There is also a small typo on line 181. Instead of a comma, use a full stop, and on line 194, use a capital letter "Molecular Simulations".
- Corrected
- On page 9, The legend of figure 2 needs to be rewritten as it does not explain the figure and is confusing.
- Corrected
- Concerning the legend of Table 2, please don't use a capital çetter in the word "Research" om line 219, and delete the word "rigourously" on line 220.
- Corrected
- Once again avoid the word "bug" in the table, convey with the rules for the scientific names, for example, not "E. Coli" but "E. coli", and in italics everywhere. On 13th line I believe that you should delete the word "Stu".
- Corrected and uniformly updated
- Please make all the above mentioned corrections into the scientific names on Table 3, too.
- Corrected and uniformly updated
- In the discussion section, page 20,line 234, you should correct the scientific names.
- Corrected
- On line 238 change the word "im-permeability" to "impermeability".
- corrected
- On line240 I would begin the sentence like this: "Furthermore, it has (...)".
- Corrected
- The section "2.1. Conclusive remarks" should be renamed "Concluding remarks", and, as I said before, it should be shortened.
- Suitable modifications have been made. The conclusion is an essential component of the manuscript, clarifying and enhancing its overall quality.
Round 2
Reviewer 2 Report
The author have answered to all the qustions raised by me
