Journal
NATURE GENETICS
Volume 47, Issue 6, Pages 632-639Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3281
Keywords
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Categories
Funding
- Wellcome Trust
- Wellcome Trust award [098051]
- Wellcome Trust research fellowship [WT092152MA]
- Wellcome Trust for the Malawi-Liverpool Wellcome Trust Clinical Research Programme [101113/Z/13/Z]
- Wellcome Trust Mahidol University Oxford Tropical Medicine Research Programme
- Wellcome Trust (Major Overseas Programmes-Thailand Unit Core Grant)
- European Society for Paediatric Infectious Diseases
- University of Oxford-Li Ka Shing Global Health Foundation
- Wellcome Trust [089275/H/091Z]
- National Health and Medical Research Council of Australia [1061409]
- Victorian Life Sciences Computation Initiative (VLSCI) [VR0082]
- Clinical Research Fellowship from GlaxoSmithKline
- UK Medical Research Council PhD studentship
- Institut Pasteur
- Institut de Veille Sanitaire
- French government 'Investissement d'Avenir' program (Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence) [ANR-10-LABX-62-IBEID]
- UK Medical Research Council [MR/J003999/1, G1100100/1]
- Society in Science
- Branco Weiss Fellowship
- antibiotic resistance surveillance project in the Democratic Republic of the Congo
- Belgian Directorate General of Development Cooperation [2.01]
- Institute of Tropical Medicine (Antwerp, Belgium) [2.01]
- Bill and Melinda Gates Foundation
- US National Institutes of Health-National Science Foundation Ecology and Evolution of Infectious Disease program [R01 TW009237]
- UK Biotechnology and Biological Sciences Research Council (BBSRC) [BB/J010367/1]
- UK BBSRC Zoonoses in Emerging Livestock Systems awards [BB/L017679, BB/L018926, BB/L018845]
- US National Institutes of Health grant [R01 AI099525-02]
- Royal Society [100087/Z/12/Z]
- National Institute of Allergy and Infectious Diseases of the US National Institutes of Health [R01 AI097493]
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [1330800] Funding Source: National Science Foundation
- BBSRC [BB/J010367/1, BB/L018845/1, BB/L018926/1] Funding Source: UKRI
- MRC [G9818340, G1100100] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/L018845/1, BB/J010367/1, BB/L018926/1] Funding Source: researchfish
- Medical Research Council [G9818340, G1100100, 1263989] Funding Source: researchfish
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The emergence of multidrug-resistant (MDR) typhoid is a major global health threat affecting many countries where the disease is endemic. Here whole-genome sequence analysis of 1,832 Salmonella enterica serovar Typhi (S. Typhi) identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years. Our analysis identifies numerous transmissions of H58, including multiple transfers from Asia to Africa and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our analysis indicates that H58 lineages are displacing antibiotic-sensitive isolates, transforming the global population structure of this pathogen. H58 isolates can harbor a complex MDR element residing either on transmissible IncHI1 plasmids or within multiple chromosomal integration sites. We also identify new mutations that define the H58 lineage. This phylogeographical analysis provides a framework to facilitate global management of MDR typhoid and is applicable to similar MDR lineages emerging in other bacterial species.
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