Abstract
BackgroundThe emergence of antimicrobial-resistant (AMR) strains of the important human and animal pathogen Salmonella enterica poses a growing threat to public health. Here, we studied the genome-wide evolution of 90 S. enterica AMR isolates, representing one host adapted serotype (S. Dublin) and two broad host range serotypes (S. Newport and S. Typhimurium).ResultsAMR S. Typhimurium had a large effective population size, a large and diverse genome, AMR profiles with high diversity, and frequent positive selection and homologous recombination. AMR S. Newport showed a relatively low level of diversity and a relatively clonal population structure. AMR S. Dublin showed evidence for a recent population bottleneck, and the genomes were characterized by a larger number of genes and gene ontology terms specifically absent from this serotype and a significantly higher number of pseudogenes as compared to other two serotypes. Approximately 50% of accessory genes, including specific AMR and putative prophage genes, were significantly over- or under-represented in a given serotype. Approximately 65% of the core genes showed phylogenetic clustering by serotype, including the AMR gene aac (6′)-Iaa. While cell surface proteins were shown to be the main target of positive selection, some proteins with possible functions in AMR and virulence also showed evidence for positive selection. Homologous recombination mainly acted on prophage-associated proteins.ConclusionsOur data indicates a strong association between genome content of S. enterica and serotype. Evolutionary patterns observed in S. Typhimurium are consistent with multiple emergence events of AMR strains and/or ecological success of this serotype in different hosts or habitats. Evolutionary patterns of S. Newport suggested that antimicrobial resistance emerged in one single lineage, Lineage IIC. A recent population bottleneck and genome decay observed in AMR S. Dublin are congruent with its narrow host range. Finally, our results suggest the potentially important role of positive selection in the evolution of antimicrobial resistance, host adaptation and serotype diversification in S. enterica.
Highlights
The emergence of antimicrobial-resistant (AMR) strains of the important human and animal pathogen Salmonella enterica poses a growing threat to public health
Typhimurium exhibited distinct genomic characteristics and evolutionary patterns; (ii) genome content of AMR S. enterica, including AMR genes, was strongly associated with serotype; (iii) positive selection mainly targeted genes encoding cell surface proteins and genes likely to function in virulence and antimicrobial resistance, while homologous recombination mainly acted on prophage-associated genes
Dublin showed evidence for experiencing a recent population bottleneck and genome decay, which are consistent with its narrow host range
Summary
The emergence of antimicrobial-resistant (AMR) strains of the important human and animal pathogen Salmonella enterica poses a growing threat to public health. We studied the genome-wide evolution of 90 S. enterica AMR isolates, representing one host adapted serotype Dublin) and two broad host range serotypes Salmonella enterica, the causative agent of salmonellosis, is a human and animal pathogen that causes substantial economic losses and major public health concerns worldwide [1, 2]. The emergence and global spread of antimicrobialresistant (AMR) S. enterica have further raised the public concern, as AMR S. enterica compromise the ability to treat infections in humans and animals [6, 7]. S. enterica contains > 2500 recognized serotypes, which display a broad range of epidemiological and ecological Previous studies have suggested that AMR strains of S. enterica may be more virulent than susceptible ones [8].
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