Impact of insertion sequences on convergent evolution of Shigella species.

Jane Hawkey,Bernhard Palsson,Helen Billman-Jacobe,Jonathan M Monk,Kathryn E Holt,Kathryn E Holt,Kathryn E Holt,Diarmaid Hughes

doi:10.1371/journal.pgen.1008931

Abstract

Shigella species are specialised lineages of Escherichia coli that have converged to become human-adapted and cause dysentery by invading human gut epithelial cells. Most studies of Shigella evolution have been restricted to comparisons of single representatives of each species; and population genomic studies of individual Shigella species have focused on genomic variation caused by single nucleotide variants and ignored the contribution of insertion sequences (IS) which are highly prevalent in Shigella genomes. Here, we investigate the distribution and evolutionary dynamics of IS within populations of Shigella dysenteriae Sd1, Shigella sonnei and Shigella flexneri. We find that five IS (IS1, IS2, IS4, IS600 and IS911) have undergone expansion in all Shigella species, creating substantial strain-to-strain variation within each population and contributing to convergent patterns of functional gene loss within and between species. We find that IS expansion and genome degradation are most advanced in S. dysenteriae and least advanced in S. sonnei; and using genome-scale models of metabolism we show that Shigella species display convergent loss of core E. coli metabolic capabilities, with S. sonnei and S. flexneri following a similar trajectory of metabolic streamlining to that of S. dysenteriae. This study highlights the importance of IS to the evolution of Shigella and provides a framework for the investigation of IS dynamics and metabolic reduction in other bacterial species.

Highlights

Shigellae are Gram-negative intracellular bacterial pathogens transmitted via the faecal-oral route and are the bacterial agents of dysentery [1,2]
A hallmark of this host-adaptation is the accumulation of insertion sequences (IS), which interrupt genes and cause deletions or genome rearrangements
S. flexneri and S. sonnei are endemic in human populations globally and contribute most to the dysentery disease burden [1]; S. dysenteriae is associated with epidemic bacillary dysentery [3] and S. boydii is rare and mostly restricted to the Indian sub-continent [1]

Summary

Introduction

Shigellae are Gram-negative intracellular bacterial pathogens transmitted via the faecal-oral route and are the bacterial agents of dysentery [1,2]. DNA sequence analyses show that the serologically defined Shigella ‘species’ are paraphyletic members of species Escherichia coli (see Fig 1A), which have converged on similar humanadapted dysentery-associated phenotypes through parallel evolutionary processes [4,5,6,7,8]. These include gains of function via acquisition of the virulence plasmid pINV which carries genes for invasive infection including the mix-spa locus encoding a type 3 secretion system [9], and of genomic islands SHI-1, which carries several toxins [10], and SHI-2, which encodes the siderophore aerobactin as well as bactericidal and immune evasion genes

Methods

Results

Discussion

Conclusion