Evolution of Pandemic Cholera at its Global Source
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Abstract
The seventh pandemic of cholera, caused by the 7 th Pandemic El Tor Lineage (7PET) Vibrio cholerae , was previously shown to have emanated in three global waves from the Bay of Bengal, bordering Bangladesh and India. However, the respective roles of the Ganges delta and basin regions in seeding these global pandemic waves were not known. We find that while there are transmission events between Bangladesh and India, V. cholerae within the two countries has largely evolved separately over the past 20 years, contained by national borders rather than following hydrological features such as the Ganges delta and basin. Evolution within Bangladesh was distinct from that seen in India, involving rapid gain and loss of genes and mobile genetic elements, particularly those involved in phage defence. The loss/gain of these anti-phage elements mirrored loss/gain of anti-defence systems in lytic phage ICP1. Importantly, the loss of these systems was associated with increased risk of severe disease and transmission outside of Bangladesh. Here we show that the Ganges basin, falling across Bangladesh and Northern India, rather than the Ganges delta, acts as a global launch pad for pandemic disease. This completely shifts our understanding of Bangladesh as the purported global source of cholera, and the role of phage in controlling spread of lineages within the current seventh pandemic.
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This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/15043068.
Does the introduction explain the research objective?
The introduction does a good job of explaining that the study is about tracking how Vibrio cholera evolves using genomic data. However, it doesn't fully explain why this research is different from previous studies. The authors should highlight what new information they are providing that hasn't already been studied. They also need to explain why they chose these specific cholera samples and why their research focuses on certain regions. This will help readers understand the significance of their work.
Are the methods appropriate?
The methods seem appropriate, but they need more details. The study uses whole-genome sequencing and …
This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/15043068.
Does the introduction explain the research objective?
The introduction does a good job of explaining that the study is about tracking how Vibrio cholera evolves using genomic data. However, it doesn't fully explain why this research is different from previous studies. The authors should highlight what new information they are providing that hasn't already been studied. They also need to explain why they chose these specific cholera samples and why their research focuses on certain regions. This will help readers understand the significance of their work.
Are the methods appropriate?
The methods seem appropriate, but they need more details. The study uses whole-genome sequencing and phylogenetic analysis, which are standard techniques for studying bacterial evolution. However, the authors don't clearly explain how they selected their samples or if their dataset might be biased toward certain regions. It's also unclear which method they used to build their evolutionary tree, which makes it difficult to assess how reliable their conclusions are.
Are the conclusions supported by the data?
The conclusions are mostly supported by the data, but some claims need stronger evidence. The study suggests that cholera's evolution follows a clear timeline, but without a detailed time-based analysis, it's hard to confirm this. The authors also discuss antibiotic resistance, but they don't explain what pressures caused these resistance genes to develop. The paper states that genomic surveillance can help track pandemic cholera, which is true, but this is already well known. The authors should be more specific about what new insights their study provides and how it can improve cholera prevention efforts.
Are the figures and visualizations effective?
The figures are useful but need some improvements. The phylogenetic trees, which show how different cholera strains are related, do not include statistical support values, making it unclear how confident we should be in the results. The genomic maps should have clearer labels to highlight important genetic features, such as antibiotic resistance genes. Some figures are difficult to read due to small font sizes. Improving these aspects will make the data more accessible and easier to interpret.
Do the authors explain their findings and suggest next steps?
The discussion section could be clearer and more detailed. The authors summarize their results well, but they don't explore other possible explanations for their findings. Could environmental factors, human behavior, or other influences play a role in cholera's evolution? The study also lacks clear next steps. What additional research should be done based on their findings? Should more samples be collected? Should different genetic markers be used?
Does this study contribute something new to the field?
Yes, but the novelty isn't clearly stated. The research has potential value, but without a stronger discussion on how it builds on previous studies, it may not stand out. The authors should compare their findings to past genomic studies on cholera and highlight what is new. They should also explain how their research could be applied in real-world cholera control efforts.
Does the writing need editing?
The writing is generally clear, and there are no major grammar issues. However, some sections contain unnecessary background information that could be condensed. The authors should focus on making their key findings more direct and easier to understand.
Would I recommend this preprint?
Yes, but only after major revisions. The study covers an important topic, but it needs improvements in methodology, explanation of findings, and clarity.
Is it ready for journal submission?
Not yet, major revisions are needed. Before submitting to a journal, the authors should clarify their methodology, strengthen their conclusions with better evidence, and improve their discussion by addressing alternative explanations and future research directions.
Competing interests
The author declares that they have no competing interests.
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