Journal
NATURE MICROBIOLOGY
Volume 6, Issue 3, Pages 327-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41564-020-00836-1
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Funding
- John Lennon Memorial Scholarship from the University of Liverpool
- Institute of Integrative Biology at the University of Liverpool
- AESA-RISE fellowship from the African Academy of Sciences
- BBSRC, Core Strategic Programme Grant at the Earlham Institute [BB/CSP17270/1]
- Institut Pasteur
- Sante publique
- French government's Investissement d'Avenir programme, Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' [ANR-10-LABX-62-IBEID]
- Wellcome Trust [106690/A/14/Z, 106914/Z/15/Z]
- Global Challenges Research Fund [BBS/OS/GC/000009D]
- BBSRC [BB/P006078/1, BBS/E/T/000PR9819, BBS/E/T/000PR9818, BB/L007223/1] Funding Source: UKRI
- MRC [MR/R020787/1] Funding Source: UKRI
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This study identified a new lineage of nontyphoidal Salmonella, ST313 L3, which emerged in Malawi in 2016 and is closely related to variants causing gastrointestinal disease in the United Kingdom and Brazil. Genomic analysis revealed degradation events in important virulence genes in ST313 L3, a phenomenon not seen in other ST313 lineages.
Bloodstream infections caused by nontyphoidal Salmonella are a major public health concern in Africa, causing similar to 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.
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