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Genome-Based Genotyping System Developed to Trace Typhoid Fever-Causing Bacteria

NEW YORK (GenomeWeb) – Members of the International Typhoid Consortium have developed a genotyping framework for characterizing and classifying global strains of Salmonella enterica serovar Typhi (S. Typhi), the culprit behind typhoid fever.

The researchers tapped whole-genome sequence data for 1,832 S. Typhi strains originating in 63 countries. They uncovered tens of thousands of SNPs that they then used to produce a detailed phylogenetic tree for the microbe. From the S. Typhi relationships and variant patterns in this tree, they focused in on a 68-SNP set that is expected to aid investigators in tracking the source of S. Typhi during future typhoid fever outbreaks.

The team demonstrated one such application of this classification framework by sequencing and genotyping 99 travel-associated isolates that were collected in a London hospital over five years, linking more than 80 of the isolates to an apparent country of origin. The study appears online today in Nature Communications.

"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," corresponding author Vanessa Wong, a researcher affiliated with the Wellcome Trust Sanger Institute and Addenbrooke's Hospital, and her co-authors wrote.

Although methods such as pulsed-field gel electrophoresis have traditionally been used to characterize S. Typhi isolates during outbreaks in industrialized countries, the authors noted that genotyping- and whole-genome sequencing-based strategies are increasingly being used to differentiate between various S. Typhi populations.

For this study, the team's phylogenetic analyses clustered the isolates into 16 main clades and 49 sub-clades, falling into four main S. Typhi groups. For example, the analysis suggested that multidrug resistant S. Typhi isolates previously described as the H58 haplotype belonged to one sub-clade. And although some clades turned up on more than one continent, the phylogenetic information revealed geography-related clade distribution differences.

From the more than 22,000 chromosomal SNPs they detected in the core S. Typhi genome, the researchers dug down to a set of 68 SNPs that appeared to differentiate between these phylogenetic groups, clades, and sub-clades.

When they applied this framework to 99 S. Typhi isolates collected between 2005 and 2010 at an East London hospital, the researchers tracked down more than a dozen genotypes that could be used to trace 81 of the S. Typhi cases back to countries in South Asia, Africa, or Oceania. Based on the SNP, sequence, and epidemiological data at hand, the other 18 cases were deemed non-travel-related.

Wong and her co-authors noted that "while ongoing surveillance in [typhoid fever] endemic areas is undoubtedly important, the use of clinically well-characterized travel-associated organisms isolated in non-endemic countries may also provide a valuable source for improving the granularity of data in the framework for genome-based surveillance of S. Typhi."

They also encouraged continued sequencing of S. Typhi isolates collected more recently than those included in the current whole-genome sequence collection.