Spatiotemporal persistence of multiple, diverse clades and toxins of Corynebacterium diphtheriae

Robert C. Will; Thandavarayan Ramamurthy; Naresh Chand Sharma; Balaji Veeraraghavan; Lucky Sangal; Pradeep Haldar; Agila Kumari Pragasam; Karthick Vasudevan; Dhirendra Kumar; Bhabatosh Das; Eva Heinz; Vyacheslav Melnikov; Stephen Baker; Vartul Sangal; Gordon Dougan; Ankur Mutreja

doi:10.1038/s41467-021-21870-5

Spatiotemporal persistence of multiple, diverse clades and toxins of Corynebacterium diphtheriae

Robert C. Will, Thandavarayan Ramamurthy, Naresh Chand Sharma, Balaji Veeraraghavan, Lucky Sangal, Pradeep Haldar, Agila Kumari Pragasam, Karthick Vasudevan, Dhirendra Kumar, Bhabatosh Das, Eva Heinz, Vyacheslav Melnikov, Stephen Baker, Vartul Sangal, Gordon Dougan, Ankur Mutreja^*

^*Corresponding author for this work

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Abstract

Diphtheria is a respiratory disease caused by the bacterium Corynebacterium diphtheriae. Although the development of a toxin-based vaccine in the 1930s has allowed a high level of control over the disease, cases have increased in recent years. Here, we describe the genomic variation of 502 C. diphtheriae isolates across 16 countries and territories over 122 years. We generate a core gene phylogeny and determine the presence of antimicrobial resistance genes and variation within the tox gene of 291 tox+ isolates. Numerous, highly diverse clusters of C. diphtheriae are observed across the phylogeny, each containing isolates from multiple countries, regions and time of isolation. The number of antimicrobial resistance genes, as well as the breadth of antibiotic resistance, is substantially greater in the last decade than ever before. We identified and analysed 18 tox gene variants, with mutations estimated to be of medium to high structural impact.

Original language	English
Article number	1500
Number of pages	8
Journal	Nature Communications
Volume	12
Issue number	1
Early online date	8 Mar 2021
DOIs	https://doi.org/10.1038/s41467-021-21870-5
Publication status	Published - 1 Dec 2021

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SDG 3 Good Health and Well-being

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Will, R. C., Ramamurthy, T., Sharma, N. C., Veeraraghavan, B., Sangal, L., Haldar, P., Pragasam, A. K., Vasudevan, K., Kumar, D., Das, B., Heinz, E., Melnikov, V., Baker, S., Sangal, V., Dougan, G., & Mutreja, A. (2021). Spatiotemporal persistence of multiple, diverse clades and toxins of Corynebacterium diphtheriae. Nature Communications, 12(1), Article 1500. https://doi.org/10.1038/s41467-021-21870-5

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title = "Spatiotemporal persistence of multiple, diverse clades and toxins of Corynebacterium diphtheriae",

abstract = "Diphtheria is a respiratory disease caused by the bacterium Corynebacterium diphtheriae. Although the development of a toxin-based vaccine in the 1930s has allowed a high level of control over the disease, cases have increased in recent years. Here, we describe the genomic variation of 502 C. diphtheriae isolates across 16 countries and territories over 122 years. We generate a core gene phylogeny and determine the presence of antimicrobial resistance genes and variation within the tox gene of 291 tox+ isolates. Numerous, highly diverse clusters of C. diphtheriae are observed across the phylogeny, each containing isolates from multiple countries, regions and time of isolation. The number of antimicrobial resistance genes, as well as the breadth of antibiotic resistance, is substantially greater in the last decade than ever before. We identified and analysed 18 tox gene variants, with mutations estimated to be of medium to high structural impact.",

author = "Will, \{Robert C.\} and Thandavarayan Ramamurthy and Sharma, \{Naresh Chand\} and Balaji Veeraraghavan and Lucky Sangal and Pradeep Haldar and Pragasam, \{Agila Kumari\} and Karthick Vasudevan and Dhirendra Kumar and Bhabatosh Das and Eva Heinz and Vyacheslav Melnikov and Stephen Baker and Vartul Sangal and Gordon Dougan and Ankur Mutreja",

note = "Funding information: The authors thank Prof. P.A. Hoskisson, and Z.A. Dyson for their expert knowledge and advice. This work primarily received funding from the Medical Research Council under the University of Cambridge Medical Research Council Doctoral Training Programme. Additionally, the Horizon 2020-MSCA-IF-2018; 843405-DIFTERIA. This research was supported by the NIHR Cambridge Biomedical Research Centre and AMR Research Capital Funding Scheme [NIHR200640]. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.",

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Will, RC, Ramamurthy, T, Sharma, NC, Veeraraghavan, B, Sangal, L, Haldar, P, Pragasam, AK, Vasudevan, K, Kumar, D, Das, B, Heinz, E, Melnikov, V, Baker, S, Sangal, V, Dougan, G & Mutreja, A 2021, 'Spatiotemporal persistence of multiple, diverse clades and toxins of Corynebacterium diphtheriae', Nature Communications, vol. 12, no. 1, 1500. https://doi.org/10.1038/s41467-021-21870-5

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T1 - Spatiotemporal persistence of multiple, diverse clades and toxins of Corynebacterium diphtheriae

AU - Will, Robert C.

AU - Ramamurthy, Thandavarayan

AU - Sharma, Naresh Chand

AU - Veeraraghavan, Balaji

AU - Sangal, Lucky

AU - Haldar, Pradeep

AU - Pragasam, Agila Kumari

AU - Vasudevan, Karthick

AU - Kumar, Dhirendra

AU - Das, Bhabatosh

AU - Heinz, Eva

AU - Melnikov, Vyacheslav

AU - Baker, Stephen

AU - Sangal, Vartul

AU - Dougan, Gordon

AU - Mutreja, Ankur

N1 - Funding information: The authors thank Prof. P.A. Hoskisson, and Z.A. Dyson for their expert knowledge and advice. This work primarily received funding from the Medical Research Council under the University of Cambridge Medical Research Council Doctoral Training Programme. Additionally, the Horizon 2020-MSCA-IF-2018; 843405-DIFTERIA. This research was supported by the NIHR Cambridge Biomedical Research Centre and AMR Research Capital Funding Scheme [NIHR200640]. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

PY - 2021/12/1

Y1 - 2021/12/1

N2 - Diphtheria is a respiratory disease caused by the bacterium Corynebacterium diphtheriae. Although the development of a toxin-based vaccine in the 1930s has allowed a high level of control over the disease, cases have increased in recent years. Here, we describe the genomic variation of 502 C. diphtheriae isolates across 16 countries and territories over 122 years. We generate a core gene phylogeny and determine the presence of antimicrobial resistance genes and variation within the tox gene of 291 tox+ isolates. Numerous, highly diverse clusters of C. diphtheriae are observed across the phylogeny, each containing isolates from multiple countries, regions and time of isolation. The number of antimicrobial resistance genes, as well as the breadth of antibiotic resistance, is substantially greater in the last decade than ever before. We identified and analysed 18 tox gene variants, with mutations estimated to be of medium to high structural impact.

AB - Diphtheria is a respiratory disease caused by the bacterium Corynebacterium diphtheriae. Although the development of a toxin-based vaccine in the 1930s has allowed a high level of control over the disease, cases have increased in recent years. Here, we describe the genomic variation of 502 C. diphtheriae isolates across 16 countries and territories over 122 years. We generate a core gene phylogeny and determine the presence of antimicrobial resistance genes and variation within the tox gene of 291 tox+ isolates. Numerous, highly diverse clusters of C. diphtheriae are observed across the phylogeny, each containing isolates from multiple countries, regions and time of isolation. The number of antimicrobial resistance genes, as well as the breadth of antibiotic resistance, is substantially greater in the last decade than ever before. We identified and analysed 18 tox gene variants, with mutations estimated to be of medium to high structural impact.

UR - https://www.scopus.com/pages/publications/85102536837

U2 - 10.1038/s41467-021-21870-5

DO - 10.1038/s41467-021-21870-5

M3 - Article

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1500

ER -

Spatiotemporal persistence of multiple, diverse clades and toxins of Corynebacterium diphtheriae

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