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.
Highlights
Accurate and reliable characterisation of bacterial pathogens is crucial for classifying related strains into clusters for both short- and long-term epidemiology
We demonstrate the application of multilevel genome typing (MGT) using Salmonella enterica serovar Typhimurium (STM), which is the single largest cause of salmonellosis in Australia and one of the most prevalent serovars in many other areas of the world including Europe [25]
We propose a set of methodologically connected multilocus sequence typing (MLST) schemes, individually called levels, that offer a gradient of resolutions for the comparison of isolates (Figure 1A)
Summary
Accurate and reliable characterisation of bacterial pathogens is crucial for classifying related strains into clusters for both short- and long-term epidemiology. In long-term epidemiology, the tracking of bacterial clones, which may share characteristics such as antimicrobial resistance or increased pathogenicity, has been vital for understanding the population dynamics of pathogens [3,4] Both are important to public health but have been performed using a plethora of separate, albeit related, tools with differing resolutions [5,6]. An ST is a stable and standardised identifier of a group of related strains, and numerous studies have used STs to track clones within a species that share important characteristics [8,9,10] Both long- and short-term epidemiology are fundamental to disease control and require accurate bacterial typing. Typhimurium, the results here suggest that MGT could form the basis for typing systems in other similar microorganisms
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