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A Vibrio cholerae Core Genome Multilocus Sequence Typing Scheme To Facilitate the Epidemiological Study of Cholera

Kevin Y. H. Liang, Fabini D. Orata, Mohammad Tarequl Islam, Tania Nasreen, Munirul Alam, Cheryl L. Tarr, Yann F. Boucher
Yves V. Brun, Editor
Kevin Y. H. Liang
aDepartment of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada
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Fabini D. Orata
aDepartment of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada
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Mohammad Tarequl Islam
aDepartment of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada
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Tania Nasreen
aDepartment of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada
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Munirul Alam
bInfectious Diseases Division, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh
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Cheryl L. Tarr
cEnteric Diseases Laboratory Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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Yann F. Boucher
aDepartment of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada
dSaw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
eSingapore Center for Environmental Life Sciences Engineering, National University of Singapore, Singapore, Singapore
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Yves V. Brun
University of Montreal
Roles: Editor
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DOI: 10.1128/JB.00086-20
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ABSTRACT

Core genome multilocus sequence typing (cgMLST) has gained popularity in recent years in epidemiological research and subspecies-level classification. cgMLST retains the intuitive nature of traditional MLST but offers much greater resolution by utilizing significantly larger portions of the genome. Here, we introduce a cgMLST scheme for Vibrio cholerae, a bacterium abundant in marine and freshwater environments and the etiologic agent of cholera. A set of 2,443 core genes ubiquitous in V. cholerae were used to analyze a comprehensive data set of 1,262 clinical and environmental strains collected from 52 countries, including 65 newly sequenced genomes in this study. We established a sublineage threshold based on 133 allelic differences that creates clusters nearly identical to traditional MLST types, providing backwards compatibility to new cgMLST classifications. We also defined an outbreak threshold based on seven allelic differences that is capable of identifying strains from the same outbreak and closely related isolates that could give clues on outbreak origin. Using cgMLST, we confirmed the South Asian origin of modern epidemics and identified clustering affinity among sublineages of environmental isolates from the same geographic origin. Advantages of this method are highlighted by direct comparison with existing classification methods, such as MLST and single-nucleotide polymorphism-based methods. cgMLST outperforms all existing methods in terms of resolution, standardization, and ease of use. We anticipate this scheme will serve as a basis for a universally applicable and standardized classification system for V. cholerae research and epidemiological surveillance in the future. This cgMLST scheme is publicly available on PubMLST (https://pubmlst.org/vcholerae/).

IMPORTANCE Toxigenic Vibrio cholerae isolates of the O1 and O139 serogroups are the causative agents of cholera, an acute diarrheal disease that plagued the world for centuries, if not millennia. Here, we introduce a core genome multilocus sequence typing scheme for V. cholerae. Using this scheme, we have standardized the definition for subspecies-level classification, facilitating global collaboration in the surveillance of V. cholerae. In addition, this typing scheme allows for quick identification of outbreak-related isolates that can guide subsequent analyses, serving as an important first step in epidemiological research. This scheme is also easily scalable to analyze thousands of isolates at various levels of resolution, making it an invaluable tool for large-scale ecological and evolutionary analyses.

FOOTNOTES

    • Received 18 February 2020.
    • Accepted 7 June 2020.
    • Accepted manuscript posted online 15 June 2020.
  • Supplemental material is available online only.

  • Copyright © 2020 American Society for Microbiology.

All Rights Reserved.

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A Vibrio cholerae Core Genome Multilocus Sequence Typing Scheme To Facilitate the Epidemiological Study of Cholera
Kevin Y. H. Liang, Fabini D. Orata, Mohammad Tarequl Islam, Tania Nasreen, Munirul Alam, Cheryl L. Tarr, Yann F. Boucher
Journal of Bacteriology Nov 2020, 202 (24) e00086-20; DOI: 10.1128/JB.00086-20

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A Vibrio cholerae Core Genome Multilocus Sequence Typing Scheme To Facilitate the Epidemiological Study of Cholera
Kevin Y. H. Liang, Fabini D. Orata, Mohammad Tarequl Islam, Tania Nasreen, Munirul Alam, Cheryl L. Tarr, Yann F. Boucher
Journal of Bacteriology Nov 2020, 202 (24) e00086-20; DOI: 10.1128/JB.00086-20
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KEYWORDS

Vibrio cholerae
whole-genome sequencing
cgMLST
cholera
core genome
epidemiological surveillance
gene-by-gene approach
multilocus sequence typing

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