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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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).
The authors declare no competing financial interests.
Supplementary Figures 1–12, Supplementary Note, Supplementary References. (PDF 13377 kb)
Epidemiological data. (XLSX 77 kb)
Frequency, association scores and direction of association for significant kmers identified in Australasian and Southeast Asian GWAS analyses. (TXT 8024 kb)
Raw kmer sequences. (TXT 8583 kb)
Coding sequences found in region-specific loci; summary data of all annotated coding sequences located in 468 Australasia- and 14 Southeast Asia-specific loci. (TXT 199 kb)
COG, GO and pathway terms with significant kmer enrichment. (XLSX 88 kb)
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Chewapreecha, C., Holden, M., Vehkala, M. et al. Global and regional dissemination and evolution of Burkholderia pseudomallei. Nat Microbiol 2, 16263 (2017). https://doi.org/10.1038/nmicrobiol.2016.263
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