Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events

Vanessa K. Wong*, Stephen Baker, Derek J. Pickard, Julian Parkhill, Andrew J. Page, Nicholas A. Feasey, Robert A. Kingsley, Nicholas R. Thomson, Jacqueline A. Keanel, Francois-Xavier Weill, David J. Edwards, Jane Hawkey, Simon R. Harris, Alison E. Mather, Amy K. Cain, James Hadfield, Peter J. Hart, Nga Tran Vu Thieu, Elizabeth J. Klemm, Dafni A. Glinos & 54 others Robert F. Breiman, Conall H. Watson, Samuel Kariuki, Melita A. Gordon, Robert S. Heyderman, Chinyere Okoro, Jan Jacobs, Octavie Lunguya, W. John Edmunds, Chisorno Msefula, Jose A. Chabalgoity, Mike Kama, Kylie Jenkins, Shanta Dutta, Florian Marks, Josefina Campos, Corinne Thompson, Stephen Obaro, Calman A. MacLennan, Christiane Dolecek, Karen H. Keddy, Anthony M. Smith, Christopher M. Parry, Abhilasha Karkey, E. Kim Mulholland, James I. Campbell, Sabina Dongol, Buddha Basnyat, Muriel Dufour, Don Bandaranayake, Take Toleafoa Naseri, Shalini Pravin Singh, Mochammad Hatta, Paul C D Newton, Robert S. Onsare, Lupeoletalalei Isaia, David Dance, Viengmon Davong, Guy Thwaites, Lalith Wijedoru, John A. Crump, Elizabeth De Pinna, Satheesh Nair, Eric J. Nilles, Duy Pham Thanh, Paul Turner, Sona Soeng, Mary Valcanis, Joan Powling, Karolina Dimovski, Geoff Hogg, Jeremy Farrar, Kathryn E. Holt, Gordon Dougan

*Corresponding author for this work

Research output: Contribution to journalArticle

193 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)632-639
Number of pages8
JournalNature Genetics
Volume47
Issue number6
DOIs
Publication statusPublished - 2015
Externally publishedYes

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