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Multilevel genome typing: genomics-guided scalable resolution typing of microbial pathogens.

ABSTRACT: BackgroundBoth long- and short-term epidemiology are fundamental to disease control and require accurate bacterial typing. Genomic data resulting from implementation of whole genome sequencing in many public health laboratories can potentially provide highly sensitive and accurate descriptions of strain relatedness. Previous typing efforts using these data have mainly focussed on outbreak detection.AimWe aimed to develop multilevel genome typing (MGT), using consecutive multilocus sequence typing (MLST) schemes of increasing sizes, stepping up from seven-gene MLST to core genome MLST, to allow examination of genetic relatedness at multiple resolution levels.MethodsThe system was applied to Salmonella enterica serovar Typhimurium. The MLST scheme used at each step (MGT level), defined a given MGT-level specific sequence type (ST). The list of STs generated from all of these increasing MGT levels, was named a genome type (GT). Using MGT, we typed 9,096 previously characterised isolates with publicly available data.ResultsOur approach could identify previously described S. Typhimurium populations, such as the DT104 multidrug resistance lineage (GT 19-2-11) and two invasive lineages of African isolates (GT 313-2-3 and 313-2-752). Further, we showed that MGT-derived clusters can accurately distinguish five outbreaks from each other and five background isolates.ConclusionMGT provides a universal and stable nomenclature at multiple resolutions for S. Typhimurium strains and could be implemented as an internationally standardised strain identification system. While established so far only for S. Typhimurium, the results here suggest that MGT could form the basis for typing systems in other similar microorganisms.

SUBMITTER: Payne M

PROVIDER: S-EPMC7262494 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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:The initial outcome of genome sequencing is the creation of long text strings written in a four letter alphabet. The role of in silico sequence analysis is to assist biologists in the act of associating biological knowledge with these sequences, allowing investigators to make inferences and predictions that can be tested experimentally. A wide variety of software is available to the scientific community, and can be used to identify genomic objects, before predicting their biological functions. However, only a limited number of biologically interesting features can be revealed from an isolated sequence. Comparative genomics tools, on the other hand, by bringing together the information contained in numerous genomes simultaneously, allow annotators to make inferences based on the idea that evolution and natural selection are central to the definition of all biological processes. We have developed the MicroScope platform in order to offer a web-based framework for the systematic and efficient revision of microbial genome annotation and comparative analysis (http://www.genoscope.cns.fr/agc/microscope). Starting with the description of the flow chart of the annotation processes implemented in the MicroScope pipeline, and the development of traditional and novel microbial annotation and comparative analysis tools, this article emphasizes the essential role of expert annotation as a complement of automatic annotation. Several examples illustrate the use of implemented tools for the review and curation of annotations of both new and publicly available microbial genomes within MicroScope's rich integrated genome framework. The platform is used as a viewer in order to browse updated annotation information of available microbial genomes (more than 440 organisms to date), and in the context of new annotation projects (117 bacterial genomes). The human expertise gathered in the MicroScope database (about 280,000 independent annotations) contributes to improve the quality of microbial genome annotation, especially for genomes initially analyzed by automatic procedures alone.Database URLs: http://www.genoscope.cns.fr/agc/mage and http://www.genoscope.cns.fr/agc/microcyc.

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Multilevel genome typing: genomics-guided scalable resolution typing of microbial pathogens.

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