Scientists at the University of Liverpool have harnessed the combined power of genomics and epidemiology to understand how a type of Salmonella bacteria has evolved to kill hundreds of thousands of immunocompromised individuals in Africa.
Salmonella
Over the last decade, bloodstream infections (BSI) caused by nontyphoidal Salmonella (NTS) have killed approximately 650,000 people globally. Additionally, invasive NTS (iNTS) disease disproportionately impacts immunocompromised individuals. These individuals include adults with HIV and children under five with malaria, malnutrition or severe anaemia living in lower-to-middle-income countries.
A recent systematic review revealed that Salmonella was the most frequently isolated pathogen in hospitalised patients diagnosed with community-onset BSI in Africa and Asia. Approximately two-thirds of iNTS disease cases in Africa are the result of S. enterica serovar Typhimurium (S. Typhimurium). Majority of S. Typhimurium isolates from BSI in Africa have sequence type ST313. There are two distinct and tightly clustered lineages of ST313. These lineages differ from each other by 455 SNPs. Researchers have proposed antimicrobial resistance and genome degradation have contributed to the success of ST313 lineages in Africa. Nonetheless, the evolutionary trajectory of these changes are unclear.
Evolutionary events
In a new study, published in Nature Microbiology, researchers from the UK, France and Malawi, sampled two comprehensive collections of Salmonella isolated from African patients with BSI. These isolates spanned from 1966 to 2018. The researchers used this information to piece together the evolutionary journey of Salmonella in Africa.
The resulting 680 genomes sequences revealed a pan-susceptible ST313 lineage (ST313 L3) which emerged in Malawi in 2016. This lineage is closely related to ST313 variants that cause gastrointestinal disease in the UK and Brazil. Moreover, genomic analysis discovered degradation events in important virulence genes in ST313 L3. The team did not identify these events in other ST313 lineages. While ST313 L3 only recently arose in the clinic, the researchers found that this lineage is a phylogenetic intermediate between ST313 L1 and L2.
The team’s in-depth genotypic and phenotypic characterisation has identified the key loss-of-function genetic events that have occurred in a stepwise manner in S. Typhimurium across Africa. These results have shown the value of using an integrated approach to link scientific research with public health.
Professor Jay Hinton, University of Liverpool and study lead, stated:
“Through a remarkable team effort, we have removed some of the mystery about the evolution of African Salmonella. We hope that by learning how these pathogens became able to infect the human bloodstream we will be better prepared to tackle future bacterial epidemics.”
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