article · Nature Communications
Salmonella enterica serovar Typhi causes typhoid fever in humans but possesses limited DNA sequence diversity, making it difficult to distinguish individual isolates. Analysis of whole-genome sequences from nearly 2,000 isolates spanning more than 60 countries enabled the creation of an extended genotyping framework. This system is phylogenetically informative and compatible with various assay formats. The analysis reveals that the global bacterial population is highly structured into dozens of geographically restricted subclades, contrasting with the rapidly spreading H58 subclade, now designated genotype 4.3.1. The framework enables the interrogation of local pathogen populations and helps detect when the bacterium is introduced into new or previously endemic areas, while indicating likely geographical origins. It provides a standardised method for classifying clinical samples and supporting further experimental studies.
Typhoid fever remains a major public health concern, but tracking outbreaks is hampered by the low genetic variation among bacterial strains. Establishing a universal genotyping scheme helps public health officials identify the origins of local outbreaks, track international transmission routes, and better understand how specific bacterial lineages spread across different geographical regions.
The genotyping framework provides an applied surveillance and diagnostic method compatible with multiple assay platforms. Potential users include clinical diagnostics laboratories, public health monitoring agencies, and epidemiological researchers tracking disease outbreaks. Although validated across extensive international genomic datasets, the framework serves primarily as a classification standard, placing it at an applied stage ready for integration into routine surveillance and diagnostic workflows rather than as a standalone commercial product.
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The population of Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, exhibits limited DNA sequence variation, which complicates efforts to rationally discriminate individual isolates. Here we utilize data from whole-genome sequences (WGS) of nearly 2,000 isolates sourced from over 60 countries to generate a robust genotyping scheme that is phylogenetically informative and compatible with a range of assays. These data show that, with the exception of the rapidly disseminating H58 subclade (now designated genotype 4.3.1), the global S. Typhi population is highly structured and includes dozens of subclades that display geographical restriction. The genotyping approach presented here can be used to interrogate local S. Typhi populations and help identify recent introductions of S. Typhi into new or previously endemic locations, providing information on their likely geographical source. This approach can be used to classify clinical isolates and provides a universal framework for further experimental investigations.
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DOI: 10.1038/ncomms12827
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