Serotype-specific evolutionary patterns of antimicrobial-resistant Salmonella enterica

Abstract

Background The 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). Results AMR 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. Conclusions Our 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 . Electronic supplementary material The online version of this article (10.1186/s12862-019-1457-5) contains supplementary material, which is available to authorized users.

Comparative genomics reveals different population structures associated with host and geographic origin in antimicrobial-resistantSalmonella enterica

“…Such geographic association of lineages was suggested to 536 be caused by differences in prophage regions, pathogenicity islands and fimbrial operons among 537 strains from different geographic locations (Zheng et al, 2017). AMR S. Newport analyzed here 538 belong to Lineage IIC as previously reported by Liao et al (2019). Our findings suggest that within 539 this lineage, S. Newport also has a geographic structure at the SNP level.…”

Comparative genomics reveals different population structures associated with host and geographic origin in antimicrobial‐resistant Salmonella enterica

“…Genome sequence data for all 90 isolates have previously been reported (Carroll et al, 2017) and deposited in the National Center for Biotechnology Information's (NCBI) Sequence Read Archive under accession number SRP068320. Genome assembly has also been reported previously (Carroll et al, 2017, Liao et al, 2019 and assembled genomes are available at NCBI DDBJ/ENA/ GenBank under the accession numbers listed in Supporting Table S4 in Liao et al (2019). Previously reported data (Liao et al, 2019) for (i) genome annotation including identification of pseudogenes by NCBI Prokaryotic Genome Annotation Pipeline (Tatusova et al, 2016), (ii) identification of orthologous genes (non-pseudogenes) by OrthoMCL (Li et al, 2003), (iii) assignment of gene ontology (GO) and enzyme commission (EC) terms by Blast2GO v1.2.1 (Conesa et al 2005), and (iv) highquality core single-nucleotide polymorphisms (SNPs) for S. Dublin, S. Newport, and S. Typhimurium called by Cortex variant caller (Iqbal et al, 2012) were used here.…”

“…The emergence of AMR strains has been described for all three serotypes (Foley and Lynne, 2008). In our previous study of AMR S. Typhimurium, S. Newport and S. Dublin isolated from human and bovine sources in New York state (NY) and Washington state (WA), we found that it is likely that antimicrobial resistance has emerged independently in multiple S. Typhimurium lineages, as compared to single lineages of S. Newport and S. Dublin (Liao et al, 2019). Also, our initial study of these isolates revealed a strong source and geographic association with antimicrobial resistance (Carroll et al, 2017).…”

“…A previously reported set of 90 S. enterica AMR isolates representing three serotypes including Dublin (n = 21), Newport (n = 32) and Typhimurium (n = 37) collected between 2008 and 2012 (Carroll et al, 2017;Liao et al, 2019) was used for this study. Among those 90 isolates, 45 were collected from NY [Dublin (n = 8), Newport (n = 19) and Typhimurium (n = 18)] and 45 were from WA [Dublin (n = 13), Newport (n = 13) and Typhimurium (n = 19)].…”

“…Hence, genomic comparison of AMR Salmonella isolated from bovine and human hosts in NY and WA will not only provide insights into the adaption and evolution of this pathogen, but also has practical implications as genetic variation associated with different sources may allow for improved source tracking (e.g., human versus bovine sources, different geographic sources) of human disease cases and contamination events. Thus, in this study, we used a previously reported WGS data set for 90 AMR S. Dublin, S. Newport and S. Typhimurium isolates obtained from dairy cattle and humans from NY and WA (Carroll et al, 2017;Liao et al, 2019) to characterize population structure associated with host and geographic origin using comparative genomics.…”