Bloodstream infections caused by nontyphoidal Salmonella are a major public health concern in Africa, causing ~49,600 deaths every year. The most common Salmonella enterica pathovariant associated with invasive nontyphoidal Salmonella disease is Salmonella Typhimurium sequence type (ST)313. It has been proposed that antimicrobial resistance and genome degradation has contributed to the success of ST313 lineages in Africa, but the evolutionary trajectory of such changes was unclear. Here, to define the evolutionary dynamics of ST313, we sub-sampled from two comprehensive collections of Salmonella isolates from African patients with bloodstream infections, spanning 1966 to 2018. The resulting 680 genome sequences led to the discovery of a pan-susceptible ST313 lineage (ST313 L3), which emerged in Malawi in 2016 and is closely related to ST313 variants that cause gastrointestinal disease in the United Kingdom and Brazil. Genomic analysis revealed degradation events in important virulence genes in ST313 L3, which had not occurred in other ST313 lineages. Despite arising only recently in the clinic, ST313 L3 is a phylogenetic intermediate between ST313 L1 and L2, with a characteristic accessory genome. Our in-depth genotypic and phenotypic characterization identifies the crucial loss-of-function genetic events that occurred during the stepwise evolution of invasive S. Typhimurium across Africa.
Bibliographical noteFunding Information:
We thank present and former members of Lab H at the Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, including members of the Hinton and Baker groups for invaluable discussions, in particular C. Chong, M. Horsburgh, S. Owen and K. Costigan for their support, contributions and advice; the MLW clinical research programme and the Institute Pasteur for access to their Salmonella archives; P. Ashton for helpful comments on the manuscript; and R. Low for his assistance in uploading metadata to repositories. C.V.P. is supported by the John Lennon Memorial Scholarship from the University of Liverpool and a Fee Bursary Award from the Institute of Integrative Biology at the University of Liverpool. B.K. was funded by an AESA-RISE fellowship from the African Academy of Sciences. N.H. is funded by the BBSRC, Core Strategic Programme Grant at the Earlham Institute (BB/CSP17270/1). F.-X.W. and A.T.-D. are supported by the Institut Pasteur, Santé publique and the French government’s Investissement d’Avenir programme, Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (ANR-10-LABX-62-IBEID). K.S.B. is funded by a Wellcome Trust Clinical Research Career Development Fellowship (106690/A/14/Z). J.C.D.H. is funded by a Wellcome Trust Senior Investigator Award (106914/Z/15/Z). Genome sequencing was done by the Earlham Institute as part of the 10,000 Salmonella genomes project which is supported by the Global Challenges Research Fund data and resources grant (BBS/OS/ GC/000009D). Next-generation sequencing and library construction were delivered via the BBSRC National Capability in Genomics and Single Cell (BB/CCG1720/1) at Earlham Institute, by members of the Genomics Pipelines Group.
© 2020, The Author(s).
Copyright 2021 Elsevier B.V., All rights reserved.
ASJC Scopus subject areas
- Applied Microbiology and Biotechnology
- Microbiology (medical)
- Cell Biology