Whole-genome epidemiology links phage-mediated acquisition of a virulence gene to the clonal expansion of a pandemic Salmonella enterica serovar Typhimurium clone

Abstract

Epidemic and pandemic clones of bacterial pathogens with distinct characteristics continually emerge, replacing those previously dominant through mechanisms that remain poorly characterized. Here, whole-genome-sequencing-powered epidemiology linked horizontal transfer of a virulence gene, sopE, to the emergence and clonal expansion of a new epidemic Salmonella enterica serovar Typhimurium (S. Typhimurium) clone. The sopE gene is sporadically distributed within the genus Salmonella and rare in S . enterica Typhimurium lineages, but was acquired multiple times during clonal expansion of the currently dominant pandemic monophasic S. Typhimurium sequence type (ST) 34 clone. Ancestral state reconstruction and time-scaled phylogenetic analysis indicated that sopE was not present in the common ancestor of the epidemic clade, but later acquisition resulted in increased clonal expansion of sopE-containing clones that was temporally associated with emergence of the epidemic, consistent with increased fitness. The sopE gene was mainly associated with a temperate bacteriophage mTmV, but recombination with other bacteriophage and apparent horizontal gene transfer of the sopE gene cassette resulted in distribution among at least four mobile genetic elements within the monophasic S . enterica Typhimurium ST34 epidemic clade. The mTmV prophage lysogenic transfer to other S. enterica serovars in vitro was limited, but included the common pig-associated S . enterica Derby (S. Derby). This may explain mTmV in S. Derby co-circulating on farms with monophasic S. Typhimurium ST34, highlighting the potential for further transfer of the sopE virulence gene in nature. We conclude that whole-genome epidemiology pinpoints potential drivers of evolutionary and epidemiological dynamics during pathogen emergence, and identifies targets for subsequent research in epidemiology and bacterial pathogenesis.

The Spatiotemporal Dynamics and Microevolution Events That Favored the Success of the Highly Clonal Multidrug-Resistant Monophasic Salmonella Typhimurium Circulating in Europe

“…However, a Bayesian analysis focusing only on genomes with this gene could confirm the chronological sequence of events identified. Three identical copies of sopE were recently identified in the genome of the monophasic S. Typhimurium ST34 strain S01569-10 ( Tassinari et al, 2020). Two chromosomal copies of sopE gene were located in distinct prophages, designated mTmV1569 and m1569, and the third copy of the sopE gene was present in strain S01569-10 on an 81.1 Kb prophage plasmid, designated pS01569 (Tassinari et al, 2020).…”

“…The temperate prophages mTmV and mTmV2, carrying virulence sopE gene described in S. 1,4,[5],12:i:-ST34 (Petrovska et al, 2016;Tassinari et al, 2020) was also shown to lead to a clonal expansion of this clone in the UK (Tassinari et al, 2020).…”

Ecological niche adaptation of Salmonella Typhimurium U288 is associated with altered pathogenicity and reduced zoonotic potential

“…1 ,4,[5],12:i:-) ST34 rapidly emerging in pig populations around the world. 8 , 15 , 16 U288 and ST34 co-existed in the UK pig population and together accounted for around 80% of isolates. 17 Despite, approximately half of all pork consumed in the UK being from UK pig herds, 18 since its emergence U288 have rarely been isolated from human infections in the UK.…”

The Age of Phage: Friend or Foe in the New Dawn of Therapeutic and Biocontrol Applications?

“…For example, an outbreak of enteroaggregative hemorrhagic E. coli O104:H4 that led to 3,842 human infections was reported to have gained virulence through the uptake of a Stx2a virulence marker by way of a Shiga toxin-encoding bacteriophage [146]. More recently, whole-genome sequencing-based epidemiological analysis has indicated the horizontal transfer of the sopE virulence gene via temperate bacteriophage mTmV, leading to the emergence and clonal distribution of a new epidemic S. enterica Typhimurium clone [147]. The second scenario involves certain pathogenic bacteria which harbor a multitude of prophages, with each phage-encoded virulence factor contributing a small amount to the overall pathogenicity of the lysogen [92].…”