Review Article | Published:

The genomic signatures of Shigella evolution, adaptation and geographical spread

Nature Reviews Microbiology volume 14, pages 235250 (2016) | Download Citation


Shigella spp. are some of the key pathogens responsible for the global burden of diarrhoeal disease. These facultative intracellular bacteria belong to the family Enterobacteriaceae, together with other intestinal pathogens, such as Escherichia coli and Salmonella spp. The genus Shigella comprises four different species, each consisting of several serogroups, all of which show phenotypic similarity, including invasive pathogenicity. DNA sequencing suggests that this similarity results from the convergent evolution of different Shigella spp. founders. Here, we review the evolutionary relationships between Shigella spp. and E . coli, and we highlight how the genomic plasticity of these bacteria and their acquisition of a distinctive virulence plasmid have enabled the development of such highly specialized pathogens. Furthermore, we discuss the insights that genotyping and whole-genome sequencing have provided into the phylogenetics and intercontinental spread of Shigella spp.

Key points

  • All available genome data indicate that the various Shigella spp.have arisen from different ancestral Escherichia coli isolates on several independent occasions.

  • The acquisition of plasmids that encode virulence genes into numerous ancestral Shigella spp. were pivotal in their evolution as human pathogens. The possession and adaptation of these plasmids has shaped the current Shigella spp.

  • Convergent evolution, through the acquisition of mobile elements and loss of gene function, enabled Shigella spp. to become restricted to humans and exquisitely adapted to interact with the human intestinal mucosa.

  • The shift in dominance from Shigella flexneri to Shigella sonnei in economically transitioning nations warrants more in-depth studies of the evolution and epidemiology of these species.

  • There is a correlation between the global dissemination of Shigella spp. clones and acquisition of resistance to multiple antimicrobials. An antimicrobial-resistance phenotype is likely to be advantageous for the bacteria, as it would promote post-symptomatic shedding by the host and would sustain short-term transmission.

  • In comparison to S. sonnei and S. flexneri, comparatively little is currently understood about Shigella dysenteriae and Shigella boydii; this needs to be addressed to reveal the full evolutionary landscape of the genus.

  • Future laboratory research should be combined with genomics to address the survival, transmission and evolution of Shigella spp. in the environment, specifically focusing on how the environmental lifestyle can affect disease epidemiology and global public health.

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H.C.T., D.P.T. and N.R.T. are funded by the Wellcome Trust (grant 098051); K.E.H is funded by the Australian National Health and Medical Research Council (NHMRC); and S.B. is a Sir Henry Dale Fellow, funded by the Wellcome Trust and the Royal Society (grant 100087/Z/12/Z).

Author information


  1. The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, 764 Vo Van Kiet, Quan 5, Ho Chi Minh City, Vietnam.

    • Hao Chung The
    • , Duy Pham Thanh
    •  & Stephen Baker
  2. Centre for Systems Genomics, University of Melbourne.

    • Kathryn E. Holt
  3. Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Victoria 3052, Australia.

    • Kathryn E. Holt
  4. Bacterial Genomics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.

    • Nicholas R. Thomson
  5. Centre for Tropical Medicine and Global Health, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7FZ, UK.

    • Nicholas R. Thomson
    •  & Stephen Baker
  6. Department of Pathogen and Molecular Biology, The London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, UK.

    • Stephen Baker


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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Stephen Baker.


Disability adjusted life years

(DALY). A measure of overall disease burden, expressed as the cumulative number of years lost owing to ill health, disability or early death.


Groups of bacterial strains that have similar characteristics and are differentiated at the subspecies level on the basis of their distinctive pathogenicity in one or more hosts.

Lysine decarboxylation

(LDC). A reaction that is used in a biochemical test to determine the ability of a microorganism to use lysine as a source of carbon for growth. In a positive LDC test, lysine is metabolized into the amine cadaverine through the activity of the enzyme lysine decarboxylase.

Microfold cell

(M cell). A specialized epithelial cell type found in the follicle-associated epithelium of the gastrointestinal tract. Their function is to transport macromolecules and microorganisms across the epithelial barriers to the immune cells, thus inducing mucosal immunity.


The selective vesicular transport of macromolecules from one side of the cell to the other while maintaining the unique compositions of these vesicular environments.

O antigen

A repeating glycan polymer attached to the outer core in lipopolysaccharide. This structure is on the very outer surface of the bacterial cell and is therefore a target for recognition by the host immune system.


The transfer of genetic material between bacterial cells through cell-to-cell contact or by a bridge-like connection between two cells.


A mode of horizontal gene transfer whereby genetic material is transferred from one bacterium to another by a virus.


A multiprotein thread-like structure protruding from prokaryotic or eukaryotic cells that is used for motility and for the sensory perception of extracellular chemicals and temperature.


Appendages composed of the protein curlin and found on many Gram-negative and some Gram-positive bacteria. Fimbriae are used mainly for adherence to bacterial cells, host cells and abiotic surfaces.

Pathogen-associated molecular pattern

(PAMP). A set of specific molecules that are present on groups of pathogens and are recognized by the innate immune system. These conserved molecular motifs in bacteria, such as lipopolysaccharide and flagellin, are usually recognized by Toll-like receptors and other pattern-recognition receptors.


A diamine with a putrid odour. It is the product of lysine decarboxylation.


A dicarboxylic acid generated as the downstream product of tryptophan catabolism. It acts as a substrate for the biosynthesis of nicotinic acid mononucleotide and, ultimately, the formation of the coenzyme NAD.

Class II integrons

Mobile genetic elements that are capable of carrying genes, including antimicrobial-resistance genes, and integrating into bacterial chromosomes by site-specific recombination. An integron contains at least an integrase, an attachment site and a promoter. Classification is based on the type of integrase.

Pulsed-field gel electrophoresis

(PFGE). A molecular typing technique based on the migration pattern of DNA fragments of variable lengths, generated by restriction enzyme treatment, in an electrical field.

Multilocus sequence typing

(MLST). A DNA sequence-based molecular typing scheme in which each isolate is distinguished by a combination of unique alleles of housekeeping genes (by comparing their genetic variations).


Phenotypic or genotypic characteristics that are shared by a set of organisms but not inherited from a common ancestor.

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