Serratia marcescens: A Versatile Opportunistic Pathogen with Emerging Clinical and Biotechnological Significance

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Review report

The authors extensively review S. marcescens from the basic mechanisms of biofilm formation, to clinically relevant strategies of evading immune systems and therapies, and finally present challenges and future directions for the field. The review is well written and covers essential topics of S. marcescens biology as well as a range of clinically relevant insights. Early chapters are comprehensive and detailed, while later chapters (7,8,9,10) are short and rely mostly on Tables or Figures for explanations. I suggest extending the text to detail the clinical relevance and therapeutic aspects of S. marcescens biology. Overall, the review is an important addition to the current literature, well written and timely.

- General remark: I suggest keeping all bacterial names in italic letters, to follow the conventions of the general literature both in extended and in abbreviated forms (e.g., full: Escherichia coli, abb: S. marcescens, E. coli).

- I think Section 2 could benefit from having Brightfield microscopy images of S. marcescens as well as a plate showing the typical red colonies that his bacteria form. This can connect the reader closer to the descriptions in the text, and the works where the images are taken from should be cited.

- Figure 2 (bottom panel): This figure is somewhat confusing. Left panel’s labels are mixed between the actual T6SS components and their locations. Also “Cell membra” is unfinished.

I suggest to present the complex’ parts : Sneath, Tube, Baseplate, Membrane Core complex, and Spike, and then combine that with the regions of the cell where this is found. Position the complex within the membrane itself for the reader to understand how the T6SS complex works here.

-Figure 2 (bottom right panel): these delivery methods in the figure are very unintuitive. Present T6SS delivery as a one delivery method, and make sizes more appropriate with an eventual zoom to cell to cell contacts showing T6SS, and secretion delivery separate. Label the figure accordingly

-Figure 2 (bottom right panel): Serratia marcescens is written in mixed italics and regular letters. Make it uniform.

- Figure 3: panels and letters appear compressed.

- Line 307-309: this has been repeated many many times. Perhaps no need to include this explanation again.

- Section 7 should be improved. This bacterium is significant in biotechnology applications and the current uses, as well as the potential further developments in biotechnology should be presented (in the text, not just in a figure legend). Particularly the productions of S. marcescens chitinase, proteases and lipases and their use in biotechnology.

- Section 8: I suggest to combine sections 7 and 8 and expand on the details of uses of enzymes and pigments of S. marcescens.

- Given the repetitive mentions of the prodigiosin, the authors should consider dedicating a small chapter in the beginning explaining the biosynthetic pathway of the pigment (as much as it is known) as well as the currently known effects of it (antimicrobial, immunosupressory, etc) and potential future applications.

Author Response

Thank you for taking the time to review our manuscript. Your careful reading and constructive suggestions improved the clarity of our argument and the strength of the review. We appreciate your expertise and the collegial tone of your feedback.

Comment 1: General remark: I suggest keeping all bacterial names in italic letters, to follow the conventions of the general literature both in extended and in abbreviated forms (e.g., full: Escherichia coli, abb: S. marcescens, E. coli).

Response 1: Revised.

 

Comment 2: I think Section 2 could benefit from having Brightfield microscopy images of S. marcescens as well as a plate showing the typical red colonies that his bacteria form. This can connect the reader closer to the descriptions in the text, and the works where the images are taken from should be cited.

Response 2: The section was revised.

 

Comment 3: Figure 2 (bottom panel): This figure is somewhat confusing. Left panel’s labels are mixed between the actual T6SS components and their locations. Also “Cell membra” is unfinished. I suggest to present the complex’ parts : Sneath, Tube, Baseplate, Membrane Core complex, and Spike, and then combine that with the regions of the cell where this is found. Position the complex within the membrane itself for the reader to understand how the T6SS complex works here.

Reponse 3: Thank you for the observation. Revised

 

Comment 4: Figure 2 (bottom right panel): these delivery methods in the figure are very unintuitive. Present T6SS delivery as a one delivery method, and make sizes more appropriate with an eventual zoom to cell to cell contacts showing T6SS, and secretion delivery separate. Label the figure accordingly

Response 4: Revised.

 

Comment 5: Figure 2 (bottom right panel): Serratia marcescens is written in mixed italics and regular letters. Make it uniform.

Response 5: Revised.

 

Comment 6: Figure 3: panels and letters appear compressed.

Response 6: Revised.

 

Comment 7: Line 307-309: this has been repeated many many times. Perhaps no need to include this explanation again.

Response 7: Excluded.

 

Comment 8: Section 7 should be improved. This bacterium is significant in biotechnology applications and the current uses, as well as the potential further developments in biotechnology should be presented (in the text, not just in a figure legend). Particularly the productions of S. marcescens chitinase, proteases and lipases and their use in biotechnology.

Response 8: Thank you, section revised.

 

Comment 9: Section 8: I suggest to combine sections 7 and 8 and expand on the details of uses of enzymes and pigments of S. marcescens.

Response 9: Sections are now combined.

 

Comment 10: Given the repetitive mentions of the prodigiosin, the authors should consider dedicating a small chapter in the beginning explaining the biosynthetic pathway of the pigment (as much as it is known) as well as the currently known effects of it (antimicrobial, immunosupressory, etc) and potential future applications.

Response 10: We tried to reorganize the mentioning of prodigiosin. We hope it is suitable now. Thank you!

Reviewer 2 Report

Comments and Suggestions for Authors

Title: Serratia marcescens: A Versatile Opportunistic Pathogen with 2 Emerging Clinical and Biotechnological Significance.

 

Similar to other pathogenic bacteria, Serratia species are emerging clinical pathogens that are known to cause infections in a broad range of human diseases. In this review, authors will cover some main points regarding this important bacterial pathogen. However, below I suggest adding/ expanding for some parts, as well as re-structure some parts into a better structure. Decision: Major Revision.

 

1. In Taxonomy and General Characteristics (Line 60). This section is very brief. Authors are encouraged to lengthen the discussion on the discovery of S. marcescens and early studies, also should mention its original classification, and indicate any taxonomic changes.
2. In line 70, author mension that “S. marcescens grows well on standard laboratory media such as nutrient agar and tryptic soy agar.”, also there are other media can be used for this purpoe please include.
3. In Virulence Factors part (Line 78). suggest to include the different factors as sub-heading (eg 3.1. Hemolysins and Cytotoxins, ………….) under the main heading 3. Virulence Factors. Also expand and add more reference (some information didn’t have references.
4. Same as the previous comment for (4. Biofilm Formation) and (5. Antibiotic Resistance). Organize to include sub-heading, and expand these parts (resistance mechanism in details).
5. in Line 280 “6. Comparative Perspective within Enterobacterales”, please add more refrences.
6. I suggest adding a section about the clinical significance of S. marcescens in humans, specifically what infections it causes (type of infections; urinary tract, respiratory, blood stream, etc.) and the severity of those infections, particularly in the immunocompromised population. This will provide a more comprehensive view of the significance of the organism.
7. in Line 305 (7. Environmental and Industrial Aspects). I suggest restructure in this part at which the heading will be "Secondary Metabolites and Functional Biomolecules of S. marcescens", and including sub-heading:1) pigmentation role (prodigiosin), in Antimicrobial Activity, Protection Against Environmental Stress, and Relation to Human Pathogenicity. This would allow a more detailed explanation of how prodigiosin contributes to the bacterium’s environmental persistence and its limited role in clinical infections. 2) Enzymes with Dual Roles in Virulence and Biotechnology (which is already in line 333). 3) siderophores.

Also include Some recent studies like:

Guryanov, I.; Naumenko, E. Bacterial Pigment Prodigiosin as Multifaceted Compound for Medical and Industrial Application. Appl. Microbiol. 2024, 4, 1702-1728. https://doi.org/10.3390/applmicrobiol4040115

Lu, Y., Liu, D., Jiang, R., Li, Z., & Gao, X. (2024). Prodigiosin: unveiling the crimson wonder - a comprehensive journey from diverse bioactivity to synthesis and yield enhancement. Frontiers in microbiology, 15, 1412776. https://doi.org/10.3389/fmicb.2024.1412776

Hamada, M.A., Mohamed, E.T. Characterization of Serratia marcescens (OK482790)’ prodigiosin along with in vitro and in silico validation for its medicinal bioactivities. BMC Microbiol 24, 495 (2024). https://doi.org/10.1186/s12866-024-03634-5

8. In Line 350, the section titled “Therapeutic Strategies and Antibiotic Options”. It is recommended that a summary of recommendations issued by the World Health Organization (WHO) over past years, with regard to antimicrobial resistance in S. marcescens be included
9. In Line 395, the section “Clinical Applications and Innovative Therapies” showed informations about bacteriophage therapy, CRISPR approaches, PAS, anti-virulence approaches and nanoparticle delivery. I suggest expanding this section with adding a subsection on natural or plant-derived therapeutic adjuncts, as several studies have demonstrated that essential oils (thymol, carvakol, eugenol) and extracts from various spices (cinnamon, clove, garlic) and phenolic phytochemicals were shown to have anti-Serratia and anti-biofilm activity. While these agents may not replace antibiotics, they may function synergistically with antibiotics, as enhancers of antibiotics' effects, quorum-sensing inhibitors, or biofilm disruptors; all consistent with the concepts of anti-virulence and adjuvant therapy that is included in the review.

Inhibitory potential of some selected essential oils and their main components on the growth and quorum-sensing based pigment production of Serratia marcescens. https://doi.org/10.24193/subbbiol.2022.2.03

Fekrirad, Z., Gattali, B., & Kashef, N. (2020). Quorum sensing-regulated functions of Serratia marcescens are reduced by eugenol. Iranian journal of microbiology, 12(5), 451–459. https://doi.org/10.18502/ijm.v12i5.4607

10. It is suggested that you include a category detailing recent developments in bioinformatics and multi-omics research examining Serratia marcescens. Generally, the fields of transcriptomics, proteomics, metabolomics, and comparative genomics (i.e., high-throughput strategies) have advanced our understandings of the adaptive capacities of this pathogen. For example, analyses of the transcriptomes of S. marcescens have documented global gene expression shifts associated with virulence, stress response, and metabolic control. Similarly, proteomic work using mass spectrometry has generated data that help identify proteins involved in pathogenicity or multi-drug resistance, or even tolerance to metals, such as reorganizing the proteome in response to manganese.

Therefore, I recommend including a separate subsection on ‘Omics-Based Insights in the Biology of S. marcescens’ that will modernize the manuscript and reflect the growing importance of bioinformatic-related discoveries in understanding the biology of this versatile pathogen.

Some examples like:

Ferreira, R. L., Parente Rocha, J. A., Leite, V. R. M. C., Moraes, D., Graziani, D., Pranchevicius, M. D. S., & Soares, C. M. A. (2025). Proteomic profile of multidrug-resistant Serratia marcescens under meropenem challenge. Microbial pathogenesis, 204, 107570. https://doi.org/10.1016/j.micpath.2025.107570

Gangadharappa, B. S., Rajashekarappa, S., & Sathe, G. (2020). Proteomic profiling of Serratia marcescens by high-resolution mass spectrometry. BioImpacts : BI, 10(2), 123–135. https://doi.org/10.34172/bi.2020.15

D'Souza, S. E., Khan, K., & Uddin, R. (2023). Proteogenomic analysis of Serratia marcescens using computational subtractive genomics approach. PloS one, 18(4), e0283993. https://doi.org/10.1371/journal.pone.0283993

11. please write Serratia marcescens (S. marcescens), then use S. marcescens
12. All bacterial names should be written in italic.
13. Please put all abbreviations used at the end under Abbreviation section.

 

Author Response

We are grateful for your detailed comments. They helped identify gaps in our methods and presentation, and guided revisions that strengthened the manuscript. Thank you for a thorough and thoughtful review.

Comment 1: In Taxonomy and General Characteristics (Line 60). This section is very brief. Authors are encouraged to lengthen the discussion on the discovery of S. marcescens and early studies, also should mention its original classification, and indicate any taxonomic changes.

Response 1: Please check line 60, we lengthened the section.

 

Comment 2: In line 70, author mension that “S. marcescens grows well on standard laboratory media such as nutrient agar and tryptic soy agar.”, also there are other media can be used for this purpoe please include.

Response 2: We added another laboratory media.

 

Comment 3: In Virulence Factors part (Line 78). suggest to include the different factors as sub-heading (eg 3.1. Hemolysins and Cytotoxins, ………….) under the main heading 3. Virulence Factors. Also expand and add more reference (some information didn’t have references.

Response 3: We find it easier to read like it is now rather than making so many subheadings. Section developed.

 

Comment 4: Same as the previous comment for (4. Biofilm Formation) and (5. Antibiotic Resistance). Organize to include sub-heading, and expand these parts (resistance mechanism in details).

Response 4: Section developed.

 

Comment 5: in Line 280 “6. Comparative Perspective within Enterobacterales”, please add more refrences.

Response 5: Added.

 

Comment 6: I suggest adding a section about the clinical significance of S. marcescens in humans, specifically what infections it causes (type of infections; urinary tract, respiratory, blood stream, etc.) and the severity of those infections, particularly in the immunocompromised population. This will provide a more comprehensive view of the significance of the organism.

Response 6: Developed in section 10.

 

Comment 7: in Line 305 (7. Environmental and Industrial Aspects). I suggest restructure in this part at which the heading will be "Secondary Metabolites and Functional Biomolecules of S. marcescens", and including sub-heading:1) pigmentation role (prodigiosin), in Antimicrobial Activity, Protection Against Environmental Stress, and Relation to Human Pathogenicity. This would allow a more detailed explanation of how prodigiosin contributes to the bacterium’s environmental persistence and its limited role in clinical infections. 2) Enzymes with Dual Roles in Virulence and Biotechnology (which is already in line 333). 3) siderophores.

Also include Some recent studies like:

Guryanov, I.; Naumenko, E. Bacterial Pigment Prodigiosin as Multifaceted Compound for Medical and Industrial Application. Appl. Microbiol. 2024, 4, 1702-1728. https://doi.org/10.3390/applmicrobiol4040115

Lu, Y., Liu, D., Jiang, R., Li, Z., & Gao, X. (2024). Prodigiosin: unveiling the crimson wonder - a comprehensive journey from diverse bioactivity to synthesis and yield enhancement. Frontiers in microbiology, 15, 1412776. https://doi.org/10.3389/fmicb.2024.1412776

Hamada, M.A., Mohamed, E.T. Characterization of Serratia marcescens (OK482790)’ prodigiosin along with in vitro and in silico validation for its medicinal bioactivities. BMC Microbiol 24, 495 (2024). https://doi.org/10.1186/s12866-024-03634-5

Response 7: The suggested studies are now discussed in section 7.

 

Comment 8: In Line 350, the section titled “Therapeutic Strategies and Antibiotic Options”. It is recommended that a summary of recommendations issued by the World Health Organization (WHO) over past years, with regard to antimicrobial resistance in S. marcescens be included

Response 8: Please check section 8.

 

Comment 9: In Line 395, the section “Clinical Applications and Innovative Therapies” showed informations about bacteriophage therapy, CRISPR approaches, PAS, anti-virulence approaches and nanoparticle delivery. I suggest expanding this section with adding a subsection on natural or plant-derived therapeutic adjuncts, as several studies have demonstrated that essential oils (thymol, carvakol, eugenol) and extracts from various spices (cinnamon, clove, garlic) and phenolic phytochemicals were shown to have anti-Serratia and anti-biofilm activity. While these agents may not replace antibiotics, they may function synergistically with antibiotics, as enhancers of antibiotics' effects, quorum-sensing inhibitors, or biofilm disruptors; all consistent with the concepts of anti-virulence and adjuvant therapy that is included in the review.

Inhibitory potential of some selected essential oils and their main components on the growth and quorum-sensing based pigment production of Serratia marcescens. https://doi.org/10.24193/subbbiol.2022.2.03

Fekrirad, Z., Gattali, B., & Kashef, N. (2020). Quorum sensing-regulated functions of Serratia marcescens are reduced by eugenol. Iranian journal of microbiology, 12(5), 451–459. https://doi.org/10.18502/ijm.v12i5.4607

Response 9: Developed.

 

Comment 10: It is suggested that you include a category detailing recent developments in bioinformatics and multi-omics research examining Serratia marcescens. Generally, the fields of transcriptomics, proteomics, metabolomics, and comparative genomics (i.e., high-throughput strategies) have advanced our understandings of the adaptive capacities of this pathogen. For example, analyses of the transcriptomes of S. marcescens have documented global gene expression shifts associated with virulence, stress response, and metabolic control. Similarly, proteomic work using mass spectrometry has generated data that help identify proteins involved in pathogenicity or multi-drug resistance, or even tolerance to metals, such as reorganizing the proteome in response to manganese.

Therefore, I recommend including a separate subsection on ‘Omics-Based Insights in the Biology of S. marcescens’ that will modernize the manuscript and reflect the growing importance of bioinformatic-related discoveries in understanding the biology of this versatile pathogen.

Some examples like:

Ferreira, R. L., Parente Rocha, J. A., Leite, V. R. M. C., Moraes, D., Graziani, D., Pranchevicius, M. D. S., & Soares, C. M. A. (2025). Proteomic profile of multidrug-resistant Serratia marcescens under meropenem challenge. Microbial pathogenesis, 204, 107570. https://doi.org/10.1016/j.micpath.2025.107570

Gangadharappa, B. S., Rajashekarappa, S., & Sathe, G. (2020). Proteomic profiling of Serratia marcescens by high-resolution mass spectrometry. BioImpacts : BI, 10(2), 123–135. https://doi.org/10.34172/bi.2020.15

D'Souza, S. E., Khan, K., & Uddin, R. (2023). Proteogenomic analysis of Serratia marcescens using computational subtractive genomics approach. PloS one, 18(4), e0283993. https://doi.org/10.1371/journal.pone.0283993

Response 10: Added.

 

Comment 11: please write Serratia marcescens (S. marcescens), then use S. marcescens

Response 11: Revised

 

Comment 12: All bacterial names should be written in italic.

Response 12: Revised.

 

Comment 13: Please put all abbreviations used at the end under Abbreviation section.

Response 13: Added.

Reviewer 3 Report

Comments and Suggestions for Authors

The authors presented an interesting verview, about the bacterium Serratia marcescens. This fairly comprehensive work could be improved:
1. The authors cite two works from 2023 stating that whole-genome sequencing has been performed on some strains Serratia marcescens. However, it's the end of 2025—it would be helpful to provide reference data from modern databases indicating how many complete genome sequences have been performed for these bacteria to date. It would be useful to analyze how many genomes are of a medical issue, how many are related to industrial use, and in which cases these bacteria was an accidental discovery.
2. Latin names should be italicized throughout the manuscript.
3. Several modern papers on biofilm formation and related processes could enhance this work:

•  https://doi.org/10.1007/s42770-025-01652-7 
•    https://doi.org/10.1128/aem.01261-25

4. In Figure 3 digital designations 1, 2, 3, and 4 should be listed—they're in the notations, but the numbers are missing in the picture. The top of the figures is unclear. "Reduced permeability"—what's the difference between the top and bottom of the figure?
What does "antioxic" mean in this context?
The notations need to be explained.

5. All tables must contain references to the works from which the original data was taken.

 

Author Response

Thank you for the rigorous assessment and for pointing us to relevant literature. Your feedback challenged our assumptions and led to clearer framing and more cautious interpretation. We value the time and care you invested in this process.

Comment 1: The authors cite two works from 2023 stating that whole-genome sequencing has been performed on some strains Serratia marcescens. However, it's the end of 2025—it would be helpful to provide reference data from modern databases indicating how many complete genome sequences have been performed for these bacteria to date. It would be useful to analyze how many genomes are of a medical issue, how many are related to industrial use, and in which cases these bacteria was an accidental discovery.

Response 1: Revised. Thank you!

Comment 2: Latin names should be italicized throughout the manuscript.

Response 2: Revised.

Comment 3: Several modern papers on biofilm formation and related processes could enhance this work:

•  https://doi.org/10.1007/s42770-025-01652-7 
•    https://doi.org/10.1128/aem.01261-25

Response 3: Revised in section 4.

 

Comment 4: In Figure 3 digital designations 1, 2, 3, and 4 should be listed—they're in the notations, but the numbers are missing in the picture. The top of the figures is unclear. "Reduced permeability"—what's the difference between the top and bottom of the figure?
What does "antioxic" mean in this context?
The notations need to be explained.

Response 4: The term was revised.

 

Comment 5: All tables must contain references to the works from which the original data was taken.

Response 5: Revised. Thank you!

Reviewer 4 Report

Comments and Suggestions for Authors

The manuscript under review is devoted to the characteristics of Serratia marcescens, a known human pathogen. The authors aim to describe molecular pathogenicity in this review, so each section should include a description of the key molecular markers: Virulence Factors, Biofilm Formation, and Antibiotic Resistance. However, this information is missing from these chapters. Chapter 2: The authors provide virtually no taxonomic data and rely on 20-year-old references. This section would benefit from a discussion of the molecular markers used to type clinical isolates and the currently available typing schemes. L. 62: Replace Proteobacteria with Pseudomonadata Chapters 3 and 4 are descriptive of well-known facts; the authors need to systematize the available and actual data to highlight the emerging clinical significance and molecular pathogenicity of both virulence factors and biofilms. L. 81-82: Figure 1 lacks information on pigments and iron acquisition mechanisms. Species and genus names of bacteria, as well as gene names, should be italicized throughout the text. L. 142: In the figure, correct the name Prieumonia to Pneumonia. L. 192: Check the citation of reference 24. L. 291-293: Missing reference to article 37, 38 - check the citation. L. 346: Table 2: Add references to the primary data from which this material was obtained. L. 380: Table 3: The headings of the Antibiotic/Class and Mechanism/Target columns do not correspond to their content. Furthermore, no references to primary sources are provided. Overall, the authors should significantly revise the review and add relevant and objective data: Clinical Significance and Molecular Pathogenicity. Once the corrections have been made, the decision on whether the manuscript should be published can be made.

Author Response

Many thanks for the prompt and insightful review. 

Comment 1: Chapter 2: The authors provide virtually no taxonomic data and rely on 20-year-old references. This section would benefit from a discussion of the molecular markers used to type clinical isolates and the currently available typing schemes.

Response 1: The section is now revised.

 

Comment 2: L. 62: Replace Proteobacteria with Pseudomonadata

Response 2: Revised. Thank you for the suggestion!

 

Comment 3: Chapters 3 and 4 are descriptive of well-known facts; the authors need to systematize the available and actual data to highlight the emerging clinical significance and molecular pathogenicity of both virulence factors and biofilms.

Response 3: The sections were revised.

 

Comment 4: L. 81-82: Figure 1 lacks information on pigments and iron acquisition mechanisms. Species and genus names of bacteria, as well as gene names, should be italicized throughout the text.

Response 4: We italicized throughout the text gene names.

 

Comment 5: L. 142: In the figure, correct the name Prieumonia to Pneumonia.

Response 5: Revised.

 

Comment 6: L. 192: Check the citation of reference 24.

Response 6: Revised.

 

Comment 7: L. 291-293: Missing reference to article 37, 38 - check the citation.

Response 7: Revised.

 

Comment 8: L. 346: Table 2: Add references to the primary data from which this material was obtained.

Response 8: Revised.

 

Comment 9: L. 380: Table 3: The headings of the Antibiotic/Class and Mechanism/Target columns do not correspond to their content.

Response 9: Revised.

 

Comment 10: Furthermore, no references to primary sources are provided. Overall, the authors should significantly revise the review and add relevant and objective data: Clinical Significance and Molecular Pathogenicity. Once the corrections have been made, the decision on whether the manuscript should be published can be made.

Response 10: Revised.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Report (Major Revision)

Title: Serratia marcescens: A Versatile Opportunistic Pathogen with Emerging Clinical and Biotechnological Significance.

 

During the major revision, authors modified almost (not all) the comment. However, there are critical points which make my decision to be MAJOR REVISION again.

 

Major concern

During the revision, I realize that all the paragraphs which was suggested to be added (paragraph line 29-42, paragraph line 76-95, paragraph line 123-143, paragraph line 229-251, paragraph line 316-327, paragraph line 437-450, and paragraph line 468-487, paragraph line 560-572., paragraph line 576-589, and paragraph line 604 to line 619), seems to be AI generated. As I didn’t find attached except the similarity report. Kindly provide AI report (for all the review article) which is critical in this case.

 

Minor concern

1. line 47. Serratia marcescens (S. marcescens) then use S. marcescens in all paper
2. paragraph from line 47 to line 53. only one reference cited and it is very old. please add up to 3 more recent

Tavares-Carreon, F., De Anda-Mora, K., Rojas-Barrera, I. C., & Andrade, A. (2023). Serratia marcescens antibiotic resistance mechanisms of an opportunistic pathogen: a literature review. PeerJ, 11, e14399. https://doi.org/10.7717/peerj.14399

3. line 69 to line 71. provide a reference
4. also selective media used for serratia such as Starr, M. P., Grimont, P. A., Grimont, F., & Starr, P. B. (1976). Caprylate-thallous agar medium for selectively isolating Serratia and its utility in the clinical laboratory. Journal of clinical microbiology, 4(3), 270–276. https://doi.org/10.1128/jcm.4.3.270-276.1976
5. also recent studied on specific media can be added such as Pérez-Viso, B., Aracil-Gisbert, S., Coque, T.M. et al. Evaluation of CHROMagar™-Serratia agar, a new chromogenic medium for the detection and isolation of Serratia marcescens. Eur J Clin Microbiol Infect Dis 40, 2593–2596 (2021). https://doi.org/10.1007/s10096-021-04328-w
6. from line 151 to line 157. sentences are very brief. please expand more details and more information for each enzyme.
7. line 340 to line 343. please provide a brief definition for each mechanism.

Author Response

Comment 1: Major concern

During the revision, I realize that all the paragraphs which was suggested to be added (paragraph line 29-42, paragraph line 76-95, paragraph line 123-143, paragraph line 229-251, paragraph line 316-327, paragraph line 437-450, and paragraph line 468-487, paragraph line 560-572., paragraph line 576-589, and paragraph line 604 to line 619), seems to be AI generated. As I didn’t find attached except the similarity report. Kindly provide AI report (for all the review article) which is critical in this case.

Response 1: It is with disrespect to say this, we tried our best to include ALL the references YOU suggested. Thank you. We do not dispose of an AI recognition tool. However, it is to say we did not use. We attached a printscreen of a fragment you mentioned, that we put through Grammarly for checking. Moreover, as you can see in the scan provided by the platform with ProofigAI it mentions: "No integrity issues".

Minor concern

Comment 2: line 47. Serratia marcescens (S. marcescens) then use S. marcescens in all paper

Response 2: Revised.

 

Comment 3: paragraph from line 47 to line 53. only one reference cited and it is very old. please add up to 3 more recent

Tavares-Carreon, F., De Anda-Mora, K., Rojas-Barrera, I. C., & Andrade, A. (2023). Serratia marcescens antibiotic resistance mechanisms of an opportunistic pathogen: a literature review. PeerJ, 11, e14399. https://doi.org/10.7717/peerj.14399

Response 3: Revised.

 

Comment 4: line 69 to line 71. provide a reference

Response 4: Revised.

 

Comment 5: also selective media used for serratia such as Starr, M. P., Grimont, P. A., Grimont, F., & Starr, P. B. (1976). Caprylate-thallous agar medium for selectively isolating Serratia and its utility in the clinical laboratory. Journal of clinical microbiology, 4(3), 270–276. https://doi.org/10.1128/jcm.4.3.270-276.1976

Response 5: The reference you mentioned is very old.

 

Comment 6: also recent studied on specific media can be added such as Pérez-Viso, B., Aracil-Gisbert, S., Coque, T.M. et al. Evaluation of CHROMagar™-Serratia agar, a new chromogenic medium for the detection and isolation of Serratia marcescens. Eur J Clin Microbiol Infect Dis 40, 2593–2596 (2021). https://doi.org/10.1007/s10096-021-04328-w

Response 6: Revised.

 

Comment 7: from line 151 to line 157. sentences are very brief. please expand more details and more information for each enzyme.

Response 7: Yes, they are short because they are wanted for their schematic nature.

 

Comment 8: line 340 to line 343. please provide a brief definition for each mechanism.

Response 8: We strongly consider that it is easier to follow the manuscript in this way.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

The submitted manuscript is ready for publication in this revised form

Author Response

Thank you very much for taking the time to review our manuscript and reply. You helped us improve our manuscript.

Reviewer 4 Report

Comments and Suggestions for Authors

Overall, I am satisfied with the corrections the authors made. I would like to request further corrections regarding the correct spelling of the bacterial taxonomic names. Correct: Pseudomonadota.

Author Response

Thank you very much for your opinion, it helped us improve our manuscript.

Round 3

Reviewer 2 Report

Comments and Suggestions for Authors

Report (accept after minor revision)

Title: Serratia marcescens: A Versatile Opportunistic Pathogen with Emerging Clinical and Biotechnological Significance.

I want to start by thanking the authors for responding to my comments and for preparing a very good review which is scientifically sound. Also, I want to clarify my previous comment: when I referred to report the AI, I did not mean to suggest that the authors used AI in preparing the manuscript as there is no AI detecting tool can confirm or refuse this. My concern is for several paragraphs that contain very long, generic, or unmodified sentences, which could otherwise appear to readers as AI generated. These paragraphs need to be rewritten in order to be clear and scientifically precise.

Therefore, I recommend addressing minor points listed below to be accepted.

1. I also recommend revising the below paragraphs as to be rewritten in order to be clear and scientifically precise also would flow better if there were shorter sentences, more concise, and structured paragraphs.

• Paragraph line 105-116. “ marcescens grows well on standard laboratory media such as nutrient agar and tryptic soy agar. Colonies typically appear moist and smooth, and they can range 06 from red to off-white, depending on pigment production and incubation temperature. Prodigiosin synthesis is generally suppressed at 37 °C and is most intense at 25–30 °C [20][11]. On blood agar, colonies are usually gray and non-hemolytic, though hemolysis may occur in some strains [21,22]. This thermal regulation of pigmentation may explain why clinical isolates, adapted to human body temperature, often lack pigmentation. Fur- thermore, its environmental robustness enables it to survive in diverse and nutrient-poor conditions, including the presence of disinfectants, saline solutions, and even chlorinated water [23][12]. A noteworthy addition to media options is CHROMagar™-Serratia (CHROMagar Paris, France), a selective chromogenic medium designed for the detection and isolation of S. marcescens.”
• paragraph line 231-353. “S. marcescens forms surface-attached communities through an adhesion, maturation, and dispersal program controlled by nutrient sensing, quorum signaling, and global regulators. Type 1 fimbriae drive primary adhesion and are regulated by the cyclic AMP catabolite repression system, which modulates fimbrial expression and biofilm output in response to carbon availability [31,55]. Quorum sensing via N-acyl homoserine lactones coordinates adhesion, maturation, and sloughing dynamics in model strains such as MG1 [37]. Lipopeptide biosurfactants of the serrawettin family, including serratamolide, facilitate surface motility that couples to early biofilm expansion and can contribute hemolytic activity [34]. The matrix contains extracellular DNA, and DNase activity alters adhesion and dispersal, supporting a functional role for eDNA in Serratia biofilms [56]. Envelope-stress signaling through the Rcs phosphorelay also reshapes biofilm-related gene expression, as shown by transcriptomic analysis of clinical isolates with altered GumB, an inner-membrane Rcs regulator [57]. Recent work refines the mechanistic link between motility and biofilm maturation in S. marcescens. A 2025 study in Applied and Environmental Microbiology shows that the metalloprotease PrtA is required for robust biofilm development by promoting flagellar turnover, its proteolytic activity is essential, and loss of prtA yields thinner, less viable biofilms that can be rescued by wild type PrtA or exogenous enzyme. These data place extracellular proteolysis on the causal path from motility suppression to mature matrix architecture [58]. In parallel, a 2025 ecological synthesis integrates genomic and phenotypic traits underpinning Serratia interactions with plants, highlighting colonization determinants, secretion systems, and quorum signaling that support surface association behaviors relevant to biofilm formation in environmental niches [59]”.

2. Line 2 (Title). Serratia marcescens should be written in italic format. Also please be sure that all bacterial names across the article in italic format
3. Line 374. WHO and CDC , describe the abbreviation at first appearance then use the abbreviation
4. Line 482. WHO defined before, use the abbreviation only
5. Line 643 (Abbreviations). some abbreviation used in the article not listed in the abbreviation list such as WHO, CDC, ... . please revise
6. bacterial names in all references not in italic format. please revise in italic format

 

Author Response

Comment 1: I also recommend revising the below paragraphs as to be rewritten in order to be clear and scientifically precise also would flow better if there were shorter sentences, more concise, and structured paragraphs.

• Paragraph line 105-116. “ marcescens grows well on standard laboratory media such as nutrient agar and tryptic soy agar. Colonies typically appear moist and smooth, and they can range 06 from red to off-white, depending on pigment production and incubation temperature. Prodigiosin synthesis is generally suppressed at 37 °C and is most intense at 25–30 °C [20][11]. On blood agar, colonies are usually gray and non-hemolytic, though hemolysis may occur in some strains [21,22]. This thermal regulation of pigmentation may explain why clinical isolates, adapted to human body temperature, often lack pigmentation. Fur- thermore, its environmental robustness enables it to survive in diverse and nutrient-poor conditions, including the presence of disinfectants, saline solutions, and even chlorinated water [23][12]. A noteworthy addition to media options is CHROMagar™-Serratia (CHROMagar Paris, France), a selective chromogenic medium designed for the detection and isolation of S. marcescens.”
• paragraph line 231-353. “S. marcescens forms surface-attached communities through an adhesion, maturation, and dispersal program controlled by nutrient sensing, quorum signaling, and global regulators. Type 1 fimbriae drive primary adhesion and are regulated by the cyclic AMP catabolite repression system, which modulates fimbrial expression and biofilm output in response to carbon availability [31,55]. Quorum sensing via N-acyl homoserine lactones coordinates adhesion, maturation, and sloughing dynamics in model strains such as MG1 [37]. Lipopeptide biosurfactants of the serrawettin family, including serratamolide, facilitate surface motility that couples to early biofilm expansion and can contribute hemolytic activity [34]. The matrix contains extracellular DNA, and DNase activity alters adhesion and dispersal, supporting a functional role for eDNA in Serratia biofilms [56]. Envelope-stress signaling through the Rcs phosphorelay also reshapes biofilm-related gene expression, as shown by transcriptomic analysis of clinical isolates with altered GumB, an inner-membrane Rcs regulator [57]. Recent work refines the mechanistic link between motility and biofilm maturation in S. marcescens. A 2025 study in Applied and Environmental Microbiology shows that the metalloprotease PrtA is required for robust biofilm development by promoting flagellar turnover, its proteolytic activity is essential, and loss of prtA yields thinner, less viable biofilms that can be rescued by wild type PrtA or exogenous enzyme. These data place extracellular proteolysis on the causal path from motility suppression to mature matrix architecture [58]. In parallel, a 2025 ecological synthesis integrates genomic and phenotypic traits underpinning Serratia interactions with plants, highlighting colonization determinants, secretion systems, and quorum signaling that support surface association behaviors relevant to biofilm formation in environmental niches [59]”.

Response 1: Revised.

 

Comment 2: Line 2 (Title). Serratia marcescens should be written in italic format. Also please be sure that all bacterial names across the article in italic format

Response 2: Revised.

 

Comment 3: Line 374. WHO and CDC , describe the abbreviation at first appearance then use the abbreviation

Response 3: Revised.

 

Comment 4: Line 482. WHO defined before, use the abbreviation only

Response 4: Revised.

 

Comment 5: Line 643 (Abbreviations). some abbreviation used in the article not listed in the abbreviation list such as WHO, CDC, ... . please revise

Response 5: Revised.

 

Comment 6: bacterial names in all references not in italic format. please revise in italic format

Response 6: Revised.