Dataset Information

Concordance of SNP- and allele-based typing workflows in the context of a large-scale international Salmonella Enteritidis outbreak investigation.

ABSTRACT: A large European multi-country Salmonella enterica serovar Enteritidis outbreak associated with Polish eggs was characterized by whole-genome sequencing (WGS)-based analysis, with various European institutes using different analysis workflows to identify isolates potentially related to the outbreak. The objective of our study was to compare the output of six of these different typing workflows (distance matrices of either SNP-based or allele-based workflows) in terms of cluster detection and concordance. To this end, we analysed a set of 180 isolates coming from confirmed and probable outbreak cases, which were representative of the genetic variation within the outbreak, supplemented with 22 unrelated contemporaneous S. enterica serovar Enteritidis isolates. Since the definition of a cluster cut-off based on genetic distance requires prior knowledge on the evolutionary processes that govern the bacterial populations in question, we used a variety of hierarchical clustering methods (single, average and complete) and selected the optimal number of clusters based on the consensus of the silhouette, Dunn2, and McClain-Rao internal validation indices. External validation was done by calculating the concordance with the WGS-based case definition (SNP-address) for this outbreak using the Fowlkes-Mallows index. Our analysis indicates that with complete-linkage hierarchical clustering combined with the optimal number of clusters, as defined by three internal validity indices, the six different allele- and SNP-based typing workflows generate clusters with similar compositions. Furthermore, we show that even in the absence of coordinated typing procedures, but by using an unsupervised machine learning methodology for cluster delineation, the various workflows that are currently in use by six European public-health authorities can identify concordant clusters of genetically related S. enterica serovar Enteritidis isolates; thus, providing public-health researchers with comparable tools for detection of infectious-disease outbreaks.

SUBMITTER: Coipan CE

PROVIDER: S-EPMC7200063 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Concordance of SNP- and allele-based typing workflows in the context of a large-scale international <i>Salmonella</i> Enteritidis outbreak investigation.

Coipan Claudia E CE Dallman Timothy J TJ Brown Derek D Hartman Hassan H van der Voort Menno M van den Berg Redmar R RR Palm Daniel D Kotila Saara S van Wijk Tom T Franz Eelco E

Microbial genomics 20200226 3

A large European multi-country <i>Salmonella enterica</i> serovar Enteritidis outbreak associated with Polish eggs was characterized by whole-genome sequencing (WGS)-based analysis, with various European institutes using different analysis workflows to identify isolates potentially related to the outbreak. The objective of our study was to compare the output of six of these different typing workflows (distance matrices of either SNP-based or allele-based workflows) in terms of cluster detection ...[more]

PMID: 32101514

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Project description:Salmonella enterica serovar Enteritidis is one of the leading causes of salmonellosis in Australia. In this study, a total of 568 S. Enteritidis isolates from two Australian states across two consecutive years were analyzed and compared to international strains, using the S. Enteritidis multilevel genome typing (MGT) database, which contained 40,390 publicly available genomes from 99 countries. The Australian S. Enteritidis isolates were divided into three phylogenetic clades (A, B, and C). Clades A and C represented 16.4% and 3.5% of the total isolates, respectively, and were of local origin. Clade B accounted for 80.1% of the isolates which belonged to seven previously defined lineages but was dominated by the global epidemic lineage. At the MGT5 level, three out of five top sequence types (STs) in Australia were also top STs in Asia, suggesting that a fair proportion of Australian S. Enteritidis cases may be epidemiologically linked with Asian strains. In 2018, a large egg-associated local outbreak was caused by a recently defined clade B lineage prevalent in Europe and was closely related, but not directly linked, to three European isolates. Additionally, over half (54.8%) of predicted multidrug resistance (MDR) isolates belonged to 10 MDR-associated MGT-STs, which were also frequent in Asian S. Enteritidis . Overall, this study investigated the genomic epidemiology of S. Enteritidis in Australia, including the first large local outbreak, using MGT. The open MGT platform enables a standardized and sharable nomenclature that can be effectively applied to public health for unified surveillance of S. Enteritidis nationally and globally. IMPORTANCE Salmonella enterica serovar Enteritidis is a leading cause of foodborne infections. We previously developed a genomic typing database (MGTdb) for S. Enteritidis to facilitate global surveillance of this pathogen. In this study, we examined the genomic features of Australian S. Enteritidis using the MGTdb and found that Australian S. Enteritidis is mainly epidemiologically linked with Asian strains (especially strains carrying antimicrobial resistance genes), followed by European strains. The first large-scale egg-associated local outbreak in Australia was caused by a recently defined lineage prevalent in Europe, and three European isolates in the MGTdb were closely related but not directly linked to this outbreak. In summary, the S. Enteritidis MGTdb open platform is shown to be a potentially powerful tool for national and global public health surveillance of this pathogen.

Project description:Salmonella enterica is a leading cause of bacterial foodborne and zoonotic illnesses in the United States. For this study, we applied four different whole genome sequencing (WGS)-based subtyping methods: high quality single-nucleotide polymorphism (hqSNP) analysis, whole genome multilocus sequence typing using either all loci [wgMLST (all loci)] and only chromosome-associated loci [wgMLST (chrom)], and core genome multilocus sequence typing (cgMLST) to a dataset of isolate sequences from 9 well-characterized Salmonella outbreaks. For each outbreak, we evaluated the genomic and epidemiologic concordance between hqSNP and allele-based methods. We first compared pairwise genomic differences using all four methods. We observed discrepancies in allele difference ranges when using wgMLST (all loci), likely caused by inflated genetic variation due to loci found on plasmids and/or other mobile genetic elements in the accessory genome. Therefore, we excluded wgMLST (all loci) results from any further comparisons in the study. Then, we created linear regression models and phylogenetic tanglegrams using the remaining three methods. K-means analysis using the silhouette method was applied to compare the ability of the three methods to partition outbreak and sporadic isolate sequences. Our results showed that pairwise hqSNP differences had high concordance with cgMLST and wgMLST (chrom) allele differences. The slopes of the regressions for hqSNP vs. allele pairwise differences were 0.58 (cgMLST) and 0.74 [wgMLST (chrom)], and the slope of the regression was 0.77 for cgMLST vs. wgMLST (chrom) pairwise differences. Tanglegrams showed high clustering concordance between methods using two statistical measures, the Baker's gamma index (BGI) and cophenetic correlation coefficient (CCC), where 9/9 (100%) of outbreaks yielded BGI values ≥ 0.60 and CCCs were ≥ 0.97 across all nine outbreaks and all three methods. K-means analysis showed separation of outbreak and sporadic isolate groups with average silhouette widths ≥ 0.87 for outbreak groups and ≥ 0.16 for sporadic groups. This study demonstrates that Salmonella isolates clustered in concordance with epidemiologic data using three WGS-based subtyping methods and supports using cgMLST as the primary method for national surveillance of Salmonella outbreak clusters.

Dataset Information

Concordance of SNP- and allele-based typing workflows in the context of a large-scale international Salmonella Enteritidis outbreak investigation.

Publications

Concordance of SNP- and allele-based typing workflows in the context of a large-scale international <i>Salmonella</i> Enteritidis outbreak investigation.

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