Whole-genome sequencing unveils how African Salmonella evolved its pathogenicity

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Researchers from Public Health England  and the University of Liverpool (both UK) collaborated as part of a study that gained new insights into the how the sub-Saharan African strain Salmonella Typhimurium (ST313) evolved.

Invasive non-typhoidal (iNTS) Salmonella disease is the most common cause of bloodstream infection in sub-Saharan Africa (sSA), killing ~400,000 individuals each year. With the high prevalence of HIV in sSA the invasive disease occurs in ~5% of all cases.

The ST313 sequence type of S. Typhimurium is most commonly associated with iNTS disease. Two distinct lineages of the strain have been identified, both of which are highly resistant to antibiotics.

The study, published in Genome Medicine, analyzed whole-genome sequences of ~3,000 S. Typhimurium isolates from UK patients and discovered 2.7% (84/3147) were a less dangerous strain of ST313.

Infection with UK-ST313 generally causes a less severe gastrointestinal illness, and researchers discovered that unlike their African counterparts, the bacterial strains were susceptible to most antibiotics.

Phylogenetic analysis revealed UK ST313 isolates had significant genomic differences from sSA Salmonella. Further analysis revealed most of the genomic content from African ST313 lineage 2 was conserved in UK ST313; however, African ST313 harboured a distinctive prophage and a repertoire of antibiotic resistance genes.

“Our findings suggest that these two viruses are always found in the African ST313 Salmonella, yet never in the UK variant. Such a strong association suggests that the acquisition of these viruses may have been an important event for the development of the African strain. The UK ST313 genomes are helping us to piece together the puzzle of how the African Salmonella evolved” explained joint lead author, Siân Owen, from the University of Liverpool.

These findings highlight the presence of a strong selection pressure for certain horizontally acquired genetic elements in the African setting. It is these genetic mutations that could affect the ability of the bacteria to cause disease.

Jay Hinton, who leads the University of Liverpool research group, clarified: “Although the clinical picture of the Salmonella epidemic in Africa is well-established, little is known about the biology of the ST313 pathogen, making it harder to develop effective control strategies. This study highlights the valuable role that routine genomic sequencing here in the UK can play to improve our understanding and help tackle a really important health problem in the developing world.”

Tim Dallman, from Public Health England, added: “Identifying this novel UK population of Salmonella has only been made possible by the recent introduction of routine whole-genome sequencing of the Salmonella samples that cause human disease in England and Wales, allowing us to make important discoveries that would be missed by conventional microbiological methods.”

The research team are currently developing their findings by carrying out a detailed comparison of multiple UK and African ST313 variants to try to clarify the exact determinants for invasive disease.

Sources: Ashton PM, Owen SV, Kaindama L et al. Public health surveillance in the UK revolutionises our understanding of the invasive Salmonella Typhimurium epidemic in Africa. Genome Med. doi.org/10.1186/s13073-017-0480-7 (2017); https://news.liverpool.ac.uk/2017/10/31/uk-salmonella-cases-shed-light-african-epidemic/

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