Abstract

The sixth global cholera pandemic lasted from 1899 to 1923. However, despite widespread fear of the disease and of its negative effects on troop morale, very few soldiers in the British Expeditionary Forces contracted cholera between 1914 and 1918. Here, we have revived and sequenced the genome of NCTC 30, a 102-year-old Vibrio cholerae isolate, which we believe is the oldest publicly available live V. cholerae strain in existence. NCTC 30 was isolated in 1916 from a British soldier convalescent in Egypt. We found that this strain does not encode cholera toxin, thought to be necessary to cause cholera, and is not part of V. cholerae lineages responsible for the pandemic disease. We also show that NCTC 30, which predates the introduction of penicillin-based antibiotics, harbours a functional β-lactamase antibiotic resistance gene. Our data corroborate and provide molecular explanations for previous phenotypic studies of NCTC 30 and provide a new high-quality genome sequence for historical, non-pandemic V. cholerae.

Highlights

  • Vibrio cholerae is the aetiological agent of cholera, a severe diarrhoeal disease that has spread globally in seven pandemics since the 1800s [1]

  • Piecing together the history of cholera pandemics requires an understanding of pandemic V. cholerae lineages and a view of the more diverse non-pandemic V. cholerae that are contemporaneous with the pandemics

  • National Collection of Type Cultures (NCTC) 30 was isolated at a time when the sixth cholera pandemic was waning [2,3]

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Summary

Introduction

Vibrio cholerae is the aetiological agent of cholera, a severe diarrhoeal disease that has spread globally in seven pandemics since the 1800s [1]. A maximum-likelihood phylogeny produced from the resultant core-gene alignment of 2622 genes showed that NCTC 30 is more closely related to Vibrio cholerae sequences than to other members of the Vibrio genus, NCTC 30 is part of a clade that is separated from many of the V. cholerae in this collection (figure 1a; electronic supplementary material, table S1). Ten blaCARB-like homologues were present in our pangenome dataset (BLASTp similarity cut-off of 95%), in strains closely related to NCTC 30 as well as in the MX-3 lineage of O1 V. cholerae, isolated in Mexico during 2000 [7] (figure 3b; electronic supplementary material, table S1). This may explain why this strain, resistant to ampicillin to a greater extent than other V. cholerae, does not resist the antibiotic completely; it may be that blaCARB-like is expressed at levels sufficient to protect NCTC 30 from diffuse, low-concentration antibiotics present in an environment

Conclusion
We thank Karen Oliver and the Wellcome Sanger
Findings
Escherichia coli infection induces increased immune
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