Isolation and Characterization of a Novel Antimicrobial Compound from Streptomyces sp. with Activity Against Multidrug-Resistant Bacteria
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Introduction . Actinomycetes are familiar as abundant sources of secondary metabolites with broad industrial and pharmaceutical significance. Within this group, genera like Actinoplanes,Streptomyces, Saccharopolyspora, Amycolatopsis and Micromonospora are renowned for yielding numerous bioactive and commercially valuable compounds. The continuing emergence of multidrug resistant (MDR) pathogens has renewed interest in discovering novel metabolites that can overcome infections no longer responsive to existing antibiotics. Hypothesis. Marine environments—long considered underexplored—harbor diverse actinomycete species capable of synthesizing structurally unique and biologically potent metabolites. Aim. To discover and characterize novel antimicrobial metabolites from marine-derived actinomycetes. Methodology. A marine Streptomyces strain that was isolated from sediment samples was used in the current investigation to extract and purify a new antibacterial metabolite known as Lovfung 1. Advanced 1D/2D NMR spectroscopic investigations in conjunction with high-resolution mass spectrometry allowed for the structural elucidation of Lovfung 1. Results. Marine environments—long considered underexplored—harbor diverse actinomycete species capable of synthesizing structurally unique and biologically potent metabolites. These marine-derived compounds demonstrate a wide spectrum of potentials, including antibacterial, antifungal, anticancer, insecticidal, and enzyme-inhibitory properties. A novel antimicrobial metabolite, designated Lovfung 1, was extracted and purified from a marine Streptomyces strain collected from sediment samples. The isolated new compound demonstrated strong inhibitory activity against a clinical multidrug resistant Klebsiella isolate. Structural elucidation of Lovfung 1 was achieved using a combination of high-resolution mass spectrometry and advanced 1D/2D NMR spectroscopic analyses. Conclusion. The study successfully identified a novel antimicrobial metabolite from a marine Streptomyces with promising activity against a multidrug-resistant pathogen. To fully realize the therapeutic potential of Lovfung 1, further investigations like Structure-Activity Relationship [SAR] Studies, in-depth mechanistic studies, broad-spectrum efficacy and toxicity profiling are recommended.
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Thank you for submitting your manuscript to Access Microbiology. Unfortunately, based on two expert reviews and my own assessment, this manuscript is not suitable for publication in its current format. The main issues include; 1) No robust identification of the producing microbe 2) Not enough evidence to support the claim of a novel antimicrobial compound 3) Very limited testing of the antimicrobial properties of the isolated compound 4) Lack of methodological details In addition to the scientific limitations, the manuscript would benefit from a significant re-write to ensure all information is relevant to the data presented, that each section contains the appropriate information, and that figures are labelled appropriately.
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Comments to Author
This is a small study where the authors identified a strain of Streptomyces from marine sediment. The authors did large scale fermentations of the strain and isolated the antibacterial compound, Lovofung A. Through a combination of mass spectrometry and NMR analysis the authors determined the structure of Lovofung A and then conducted bioassays against a clinical isolate of Klebsiella. The results show Lovofung A has comparable activity to other known antibiotics and the authors comment on how this demonstrates the potential for finding novel antimicrobials from marine sediment samples. The article is generally well written, and the experimental methods are detailed. The introduction is very long, reading more like a review than a journal article, so this could benefit from some trimming. Likewise, …
Comments to Author
This is a small study where the authors identified a strain of Streptomyces from marine sediment. The authors did large scale fermentations of the strain and isolated the antibacterial compound, Lovofung A. Through a combination of mass spectrometry and NMR analysis the authors determined the structure of Lovofung A and then conducted bioassays against a clinical isolate of Klebsiella. The results show Lovofung A has comparable activity to other known antibiotics and the authors comment on how this demonstrates the potential for finding novel antimicrobials from marine sediment samples. The article is generally well written, and the experimental methods are detailed. The introduction is very long, reading more like a review than a journal article, so this could benefit from some trimming. Likewise, some of the content from the introduction, for example the discussions of other compounds isolated from marine sediment, may belong better in the discussion section. The authors note in the conclusions that further studies such as MIC and toxicity are warranted, but I think there are a few other areas where the authors could expand on the results with little/no additional experimental work required. For example, I would like to see more discussion of the structure of Lovofung A: what class of compound is it? Are there any similar molecules in the literature? Do they have comparable bioactivity? Similarly, more details on the producing strain would be welcome. Sequencing of the genome would provide details on whether it is a new strain and would also enable AntiSMASH analysis to be conducted to try to identify candidate biosynthetic gene clusters that may be responsible for the production of Lovofung A. If this is outside the scope of this work, perhaps a 16S sequence to give some information on phylogeny? Specific comments: Line 77: Check grammar here, this sentence doesn't make sense to me Line 149: This feels like a repeat of above, possible some of this could be cut down Line 176: Are the numbers in square brackets referring to structures here? Consider changing the formatting to distinguish from your references. Line 202: 16 micro what? Missing unit Line 269: Typo? Filter or Filtered Line 302: The legend for Figure 4 needs much more detail e.g. what strain is used, what do the numbers mean, what is 'S'? Where are the blanks discs/other controls mentioned in the text. A figure should stand alone with it's legend rather than relying on content from within the main body of the article. Line 343 - 375: This section reads more like the discussion than results
Please rate the manuscript for methodological rigour
Good
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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Comments to Author
This manuscript describes the production of an antibiotic active against Klebsiella sp. isolated from a marine bacterium. The manuscript is difficult to follow, it is not clear how results were interpreted, and it is missing key relevant information. Below are several suggestions, including additional experiments, that will help the authors rewrite the manuscript so that it is of a publication standard. The title is misleading. There is no evidence presented that the antimicrobial compound described in this study is novel, or that the producing organisms is a Streptomyces sp. In order to identify the producing organism as a Streptomyces sp., at least 16S sequencing should be conducted and provided, as well as a list of it's closest phylogenetic relatives. In order to determine that this is a novel …
Comments to Author
This manuscript describes the production of an antibiotic active against Klebsiella sp. isolated from a marine bacterium. The manuscript is difficult to follow, it is not clear how results were interpreted, and it is missing key relevant information. Below are several suggestions, including additional experiments, that will help the authors rewrite the manuscript so that it is of a publication standard. The title is misleading. There is no evidence presented that the antimicrobial compound described in this study is novel, or that the producing organisms is a Streptomyces sp. In order to identify the producing organism as a Streptomyces sp., at least 16S sequencing should be conducted and provided, as well as a list of it's closest phylogenetic relatives. In order to determine that this is a novel antimicrobial compound, more information is required in terms of the molecule itself, to what class this molecule belongs to etc. The abstract is too long and repetitive. Similarly, the introduction is too long, repetitive and full of information which is not relevant. For example, there is a very lengthy introduction on Staphylococcus aureus, which is not a strain that appears at all as part of the results section. The introduction needs to be concise and relevant to the aspects covered in the results of the manuscript. The methods do not provide incubation times for initial strain isolation, or why, other than based on morphology, which is not a reliable classification method, the strain was classified as a Streptomyces sp. Also, coordinates are not provided for the sediment location. There are no methods describing mass spectrometry or NMR experiments which are mentioned in the results. This need to be included and written to a standard where they can be reproduced (this applies to all methodology described). It looks like the only indicator strain used was a Klebsiella sp. clinical isolate but the heading of that methods subsection (Collection of test pathogens) implies that several were used. It would be really good to see this natural product tested against several Gram positive and Gram negative pathogens and compare activity against them. The antimicrobial test section should contain a table of all the antibiotics in the discs tested and their concentrations. The results are very difficult to follow and it is not clear if Lovfung is a complex of different molecules or a pure one, and how exactly it was purified and this was tested and confirmed. The discussion again just talks about S. aureus and other antibiotics which may or may not be similar to the one detected in this study and it is not clear why the discussion is relevant. Additionally, there are results' figures in the methods and figures are not clearly explained as they do not include legends.
Please rate the manuscript for methodological rigour
Very poor
Please rate the quality of the presentation and structure of the manuscript
Very poor
To what extent are the conclusions supported by the data?
Not at all
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
No: Non human or animal work described
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