Species-wide whole genome sequencing reveals historical global spread and recent local persistence in Shigella flexneri.

Ishrat J Azmi ,Wanderley Dias Da Silveira ,Clare R Barker ,Malika Gouali ,Alejandro Cravioto ,Kaisar A Talukder ,François‐Xavier Weill ,Karen H Keddy ,Nicholas R Thomson ,Julian Parkhill ,Lothar H Wieler ,Thomas R Connor ,Claire Jenkins ,Anthony M Smith ,Stephen Baker ,Torsten Semmler ,Duy Pham Thanh ,Kate S Baker ,Shah M Faruque ,Dong Wook Kim

doi:10.7554/elife.07335

Abstract

Shigella flexneri is the most common cause of bacterial dysentery in low-income countries. Despite this, S. flexneri remains largely unexplored from a genomic standpoint and is still described using a vocabulary based on serotyping reactions developed over half-a-century ago. Here we combine whole genome sequencing with geographical and temporal data to examine the natural history of the species. Our analysis subdivides S. flexneri into seven phylogenetic groups (PGs); each containing two-or-more serotypes and characterised by distinct virulence gene complement and geographic range. Within the S. flexneri PGs we identify geographically restricted sub-lineages that appear to have persistently colonised regions for many decades to over 100 years. Although we found abundant evidence of antimicrobial resistance (AMR) determinant acquisition, our dataset shows no evidence of subsequent intercontinental spread of antimicrobial resistant strains. The pattern of colonisation and AMR gene acquisition suggest that S. flexneri has a distinct life-cycle involving local persistence.

Highlights

Once a major cause of mortality and morbidity in Europe and the US prior to the widespread provision of reliable sanitation systems and clean drinking water, bacterial dysentery caused by Shigella spp., Connor et al eLife 2015;4:e07335
To determine a detailed phylogeny of this species we mapped the sequence reads from the 351 S. flexneri strains to the concatenated reference genome of S. flexneri strain 301, including its virulence plasmid (VP), to detect single nucleotide polymorphisms (SNPs)
Following the removal of recombinant regions, 55,662 SNPs remained in total, with 53,078 on the chromosome and 2584 on the VP

Summary

Introduction

Once a major cause of mortality and morbidity in Europe and the US prior to the widespread provision of reliable sanitation systems and clean drinking water, bacterial dysentery caused by Shigella spp., Connor et al eLife 2015;4:e07335. Epidemiology and global health | Microbiology and infectious disease eLife digest Dysentery is a disease in which the intestine becomes inflamed due to infection by bacteria, viruses or other microbes. Of the bacteria that can cause dysentery, bacteria called Shigella are most often responsible. Humans can acquire Shigella through contaminated food or water. Improvements to sanitation combined with access to clean drinking water and better food hygiene have decreased the number of cases of dysentery in many countries. The disease continues to be common in low-income countries, especially in young children

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