Epidemic multiple drug resistant Salmonella Typhimurium causing invasive disease in sub-Saharan Africa have a distinct genotype

  1. Robert A. Kingsley1,9,10,
  2. Chisomo L. Msefula2,9,
  3. Nicholas R. Thomson1,9,
  4. Samuel Kariuki1,3,
  5. Kathryn E. Holt1,
  6. Melita A. Gordon2,
  7. David Harris1,
  8. Louise Clarke1,
  9. Sally Whitehead1,
  10. Vartul Sangal4,
  11. Kevin Marsh5,
  12. Mark Achtman4,6,
  13. Malcolm E. Molyneux2,
  14. Martin Cormican7,
  15. Julian Parkhill1,
  16. Calman A. MacLennan2,8,
  17. Robert S. Heyderman2 and
  18. Gordon Dougan1
  1. 1 The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom;
  2. 2 Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi;
  3. 3 Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya;
  4. 4 Department of Molecular Biology, Max-Planck Institute for Infection Biology, D-10117 Berlin, Germany;
  5. 5 Kenya Medical Research Institute–Wellcome Trust Collaborative Project, Kilifi, Kenya;
  6. 6 Environmental Research Institute and Department of Microbiology, University College Cork, Cork, Ireland;
  7. 7 Department of Bacteriology, National University of Ireland, Galway, Ireland;
  8. 8 Medical Research Council Centre for Immune Regulation, Institute of Biomedical Research, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom

    1. ↵9 These authors contributed equally to this work.

    Abstract

    Whereas most nontyphoidal Salmonella (NTS) are associated with gastroenteritis, there has been a dramatic increase in reports of NTS-associated invasive disease in sub-Saharan Africa. Salmonella enterica serovar Typhimurium isolates are responsible for a significant proportion of the reported invasive NTS in this region. Multilocus sequence analysis of invasive S. Typhimurium from Malawi and Kenya identified a dominant type, designated ST313, which currently is rarely reported outside of Africa. Whole-genome sequencing of a multiple drug resistant (MDR) ST313 NTS isolate, D23580, identified a distinct prophage repertoire and a composite genetic element encoding MDR genes located on a virulence-associated plasmid. Further, there was evidence of genome degradation, including pseudogene formation and chromosomal deletions, when compared with other S. Typhimurium genome sequences. Some of this genome degradation involved genes previously implicated in virulence of S. Typhimurium or genes for which the orthologs in S. Typhi are either pseudogenes or are absent. Genome analysis of other epidemic ST313 isolates from Malawi and Kenya provided evidence for microevolution and clonal replacement in the field.

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    1. Published in Advance November 9, 2009, doi: 10.1101/gr.091017.109 Genome Res. 19: 2279-2287 Copyright © 2009 by Cold Spring Harbor Laboratory Press

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