PT - JOURNAL ARTICLE AU - Lijuan Luo AU - Michael Payne AU - Sandeep Kaur AU - Dalong Hu AU - Liam Cheney AU - Sophie Octavia AU - Qinning Wang AU - Mark M. Tanaka AU - Vitali Sintchenko AU - Ruiting Lan TI - Elucidation of global and local epidemiology of <em>Salmonella</em> Enteritidis through multilevel genome typing AID - 10.1101/2020.06.30.169953 DP - 2021 Jan 01 TA - bioRxiv PG - 2020.06.30.169953 4099 - http://biorxiv.org/content/early/2021/02/04/2020.06.30.169953.short 4100 - http://biorxiv.org/content/early/2021/02/04/2020.06.30.169953.full AB - Salmonella Enteritidis is a major foodborne pathogen that causes both local and international outbreaks with complex transmission pathways. Invasive infections which are associated with multidrug resistance (MDR) are an increasing concern around the globe. However, the global epidemiological picture of S. Enteritidis remains unclear. Here, using the novel multilevel genome typing (MGT) approach, we have characterised the genomic epidemiology of S. Enteritidis in unprecedented detail. We examined 26,670 publicly available S. Enteritidis whole genome sequences from 86 countries over 101 years to reveal their spatial and temporal distributions. Using MGT4 and MGT5, we identified globally prevalent and regionally restricted sequence types (STs). Source associated STs were identified, such as poultry associated MGT4-STs, which were common in human cases in the USA. Temporal trends were observed in the UK with MGT5-STs from 2014 to 2018, revealing both long lived endemic STs and the rapid expansion of new STs. Using MGT3 to MGT6, we identified MDR associated STs to facilitate tracking MDR spread. The majority of the global S. Enteritidis population fell within two predominant lineages with significant differences in geographic distribution, outbreak frequency, antimicrobial resistance and mutation rate. An online open MGT database has been established for unified international surveillance of S. Enteritidis. We demonstrated that MGT provides a flexible and high-resolution genome typing tool for S. Enteritidis surveillance and outbreak detection.Impact statement Salmonella Enteritidis is a common foodborne pathogen, causing both diarrheal and invasive infections with distinct geographic and phylogenetic distributions. Large scale international outbreaks were frequently reported in certain subtypes of S. Enteritidis. Multilocus sequence typing is a well-established strain typing method based on exact comparisons of gene sequences. It is highly desirable to develop an MLST based stable and uniform genomic nomenclature system to track and examine these high-risk genomic subtypes. In this work, a novel MLST based genomic typing scheme, Multilevel Genome Typing (MGT) was established for S. Enteritidis. The global epidemiological characteristics of S. Enteritidis were elucidated. A total of 26,670 publicly available whole genome sequences from 86 countries over 101 years were analysed: globally prevalent sequence types (STs), regionally restricted STs, large scale outbreaks, invasive infections and multidrug resistance (MDR) associated STs were identified. These STs can facilitate the identification and control of outbreaks and help tracking the spread of MDR. Moreover, we developed an online MGT database for unified global public health surveillance for S. Enteritidis.Data SummaryThe MGT database for S. Enteritidis is available at https://mgtdb.unsw.edu.au/enteritidis/.All accession numbers of the public available genomes were available in the MGT database and Data Set S1, Tab 7. And there were no newly sequenced data in this study.Supplementary material: Supplementary Fig. S1 to S7, supplementary methods and supporting results about the evaluation of potential repeat sequencing bias.Data Set S1: Supporting tables of the main results.Data Set S2. Supporting tables of the repeat sequencing bias evaluation by removing the potential repeat sequencing isolates. Note outbreak isolates may also be removed.Competing Interest StatementThe authors have declared no competing interest.MGTMultilevel genome typingSTSequence typeCCClonal complexODCOutbreak detection clusterSNPSingle nucleotide polymorphismMLSTMulti-locus sequence typingcgMLSTcore genome multi-locus sequence typingHierCCHierarchical clustering of cgMLSTARAntibiotic resistanceMDRMulti-drug resistance