Abstract

The environmental bacterium Burkholderia pseudomallei causes an estimated 165,000 cases of human melioidosis per year worldwide and is also classified as a biothreat agent. We used whole genome sequences of 469 B. pseudomallei isolates from 30 countries collected over 79 years to explore its geographic transmission. Our data point to Australia as an early reservoir, with transmission to Southeast Asia followed by onward transmission to South Asia and East Asia. Repeated reintroductions were observed within the Malay Peninsula and between countries bordered by the Mekong River. Our data support an African origin of the Central and South American isolates with introduction of B. pseudomallei into the Americas between 1650 and 1850, providing a temporal link with the slave trade. We also identified geographically distinct genes/variants in Australasian or Southeast Asian isolates alone, with virulence-associated genes being among those over-represented. This provides a potential explanation for clinical manifestations of melioidosis that are geographically restricted.

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Acknowledgements

The authors acknowledge the Wellcome Trust Sanger Institute library construction, sequence and core informatics teams and E. Blane for their technical support. The authors thank T. Nandi and P. Tan at Genome Institute of Singapore, and E. Price and D. Sarovich at Menzies School of Health Research, Australia, for providing access to publically available WGS data. The authors thank the following people who provided isolates or DNA: N. Day, MORU, Faculty of Tropical Medicine, Mahidol University; P. Newton, M. Vongsouvath, M. Mayway, V. Davong, O. Lattana, C. Moore, S. Rattanavong and the directors and staff of Mahosot Hospital, Vientiane, Lao PDR; V. Kumar, Ankor Hospital for Children, Siem Reap, Cambodia; J. Campbell, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam; H. Suk Wai, Ocean Park Corporation, Hong Kong SAR, China; C. Kham and T. Phe, Sihanouk Hospital Centre of Hope, Phnom Penh, Cambodia; J.W. Wiersinga, Academic Medical Center (AMC), Amsterdam, the Netherlands; J. Jacobs, ITM, Antwerp, Belgium; J.E. Russell, National Collection of Type Cultures, UK; T. Pitt, NHS Blood and Transplant, UK; D. Godoy, Imperial College, UK; S. Emonet, Geneva University Hospitals, Switzerland; S. Morpeth, Middlemore Hospital, New Zealand and J. Gee, CDC, USA. C.C. is a Sir Henry Wellcome post-doctoral Fellow (grant no. 107376/Z/15/Z). J.C., M.V. and Z.Y. were supported by the COIN Centre of Excellence and Z.Y. through an HIIT post-doctoral fellowship. A.E.M. is supported by a Biotechnology and Biological Sciences Research Council grant (no. BB/M014088/1). B.G.S. was supported by Wellcome Trust grant no. WT089472. D.A.B.D. and R.P. are supported by Wellcome Trust grants 106698/Z/14 and B9R00760. D.L. and V.W. are supported by Wellcome Trust grant 089275/Z/09/Z. M.M. and B.J.C. are supported by the Australian National Health and Medical Research Council through project grants 1046812 and 1098337. This publication presents independent research supported by the Health Innovation Challenge Fund (WT098600, HICF-T5-342), a parallel funding partnership between the Department of Health and the Wellcome Trust. The views expressed in this publication are those of the author(s) and not necessarily those of the Department of Health or the Wellcome Trust. This project was also funded by a grant awarded to the Wellcome Trust Sanger Institute (no. 098051).

Author information

Author notes

    • Rattanaphone Phetsouvanh

    Deceased.

Affiliations

  1. Department of Medicine, University of Cambridge, CB2 0QQ, UK

    • Claire Chewapreecha
    • , Gordon Dougan
    •  & Sharon J. Peacock
  2. Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK

    • Claire Chewapreecha
    • , Matthew T. G. Holden
    • , Simon R. Harris
    • , Gordon Dougan
    • , Julian Parkhill
    •  & Sharon J. Peacock
  3. Bioinformatics and Systems Biology Program, School of Bioresources and Technology, King Mongkut's University of Technology Thonburi, 10140 Bangkok, Thailand

    • Claire Chewapreecha
  4. School of Medicine, University of St Andrew, KY16 9AJ, UK

    • Matthew T. G. Holden
  5. Department of Mathematics and Statistics, University of Helsinki 00100, Finland

    • Minna Vehkala
    • , Zhirong Yang
    •  & Jukka Corander
  6. Department of Medical and Clinical Genetics, Genome-Scale Biology Research Program, University of Helsinki 00100, Finland

    • Niko Välimäki
  7. Department of Veterinary Medicine, University of Cambridge, CB3 0ES, UK

    • Alison E. Mather
  8. Emerging Pathogens Institute, University of Florida, Florida 32611, USA

    • Apichai Tuanyok
  9. Department of Clinical Sciences, Institute of Tropical Medicine, 2000 Antwerp, Belgium

    • Birgit De Smet
  10. Laboratory of Microbiology, Faculty of Sciences, Ghent University, 9000 Belgium

    • Birgit De Smet
  11. Department of Infection and Epidemiology, Enteric bacteria pathogen Unit, Institut Pasteur, 75015 Paris, France

    • Simon Le Hello
  12. Department of Microbiology, Collection of Institut Pasteur, Institut Pasteur, 75015 Paris, France

    • Chantal Bizet
  13. Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University and Royal Darwin Hospital, Darwin, Northern Territory 0811 Australia

    • Mark Mayo
    •  & Bart J. Currie
  14. Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 10400 Bangkok, Thailand

    • Vanaporn Wuthiekanun
    •  & Direk Limmathurotsakul
  15. Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, 10400 Bangkok, Thailand

    • Direk Limmathurotsakul
  16. Centre for Tropical Medicine & Global Health, University of Oxford, OX3 7FZ, UK

    • Direk Limmathurotsakul
    •  & David A. B. Dance
  17. Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR

    • Rattanaphone Phetsouvanh
    •  & David A. B. Dance
  18. Department of Infectious Disease Epidemiology, Imperial College, SW7 2AZ, UK

    • Brian G. Spratt
  19. Department of Biostatistics, University of Oslo, 0313 Oslo, Norway

    • Jukka Corander
  20. Center for Microbial Genetics and Genomics, Northern Arizona University, Arizona 86011-4073, USA

    • Paul Keim
  21. London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK

    • David A. B. Dance
    •  & Sharon J. Peacock

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Contributions

A.T., B.D.S., S.L.H., C.B., M.M., V.W., D.L., R.P., B.G.S., P.K., D.A.B.D. and B.J.C. collected and provided the samples for the study. C.C. designed and performed the analyses. M.T.G.H., S.R.H., A.E.M., J.C., J.P. and G.D. designed and contributed materials and analysis tools. M.V., N.V., Z.Y., and J.C. performed the kmer-based analyses in the first draft. C.C. performed the kmer-based analysis in the revised draft. Z.Y. and J.C. performed cluster analyses. S.J.P. was responsible for management of the study. S.J.P. and C.C. wrote the paper with input from all authors. All authors approved the manuscript prior to submission.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Claire Chewapreecha or Sharon J. Peacock.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    Supplementary Figures 1–12, Supplementary Note, Supplementary References.

Excel files

  1. 1.

    Supplementary Data 1

    Epidemiological data.

  2. 2.

    Supplementary Data 5

    COG, GO and pathway terms with significant kmer enrichment.

Text files

  1. 1.

    Supplementary Data 2

    Frequency, association scores and direction of association for significant kmers identified in Australasian and Southeast Asian GWAS analyses.

  2. 2.

    Supplementary Data 3

    Raw kmer sequences.

  3. 3.

    Supplementary Data 4

    Coding sequences found in region-specific loci; summary data of all annotated coding sequences located in 468 Australasia- and 14 Southeast Asia-specific loci.