Stepwise evolution of Salmonella Typhimurium ST313 causing bloodstream infection in Africa

Abstract

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.

Elucidation of global and national genomic epidemiology of Salmonella enterica serovar Enteritidis through multilevel genome typing

“…Some virulence or SPIs genes were likely to have been lost in certain STs/CCs. Loss of virulence genes had been previously observed in S. Enteritidis and S. Typhimurium [5,66]. In summary, both acquisition and loss of virulence factors occurred in the evolution of S. Enteritidis.…”

Contamination of street food with multidrug-resistant Salmonella, in Ouagadougou, Burkina Faso

“…resistant to antibiotics [ 13 ]. Some multidrug-resistant (MDR) Salmonella populations, such as the “ST198-X1” clone of serotype Kentucky [ 14 ] or the invasive clones of serotypes Enteritidis [ 15 ] and Typhimurium [ 16 ] have spread throughout Africa. Previous studies in Burkina Faso have shown that Salmonella enterica strains isolated from raw beef meat, chicken meat and faeces, and from eggs were resistant to commonly used antibiotics [ 2 , 3 , 13 ], but the genetic relationships between these strains and known MDR populations circulating at a larger scale were not assessed.…”

The prospect of orally administered monoclonal secretory IgA (SIgA) antibodies to prevent enteric bacterial infections

“…While infection normally manifests as self-limiting gastroenteritis, the emergence invasive non-typhoidal STm (iNTS) isolates such as sequence type 313 (ST313) in sub-Saharan Africa capable of causing fatal systemic infections in children and immunocompromised individuals has raised alarms. 3,4,60 Furthermore, the increase of iNTS isolates carrying resistance to one or more commonly used antibiotics has prompted investigations into vaccines and alternative biologics, such as SIgA, to prevent Salmonella infections.…”

“…2 While a leading cause of MSD, the food-and water-borne pathogen, Salmonella enterica serovar Typhimurium (STm), also deserves attention because it has emerged in parts of Saharan and sub-Saharan Africa as a cause of fatal bloodstream infections in young children. 3,4 For newborns, breastfeeding is one of the most effective defenses against diarrheal diseases. [5][6][7] Colostrum and breast milk each contain an array of bioactive compounds, including cytokines, defensins, lactoferrin, and human milk oligosaccharides that collectively hinder opportunistic and pathogenic bacteria from colonizing the neonatal intestinal epithelium.…”