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Deletion of toxin–antitoxin systems in the evolution of Shigella sonnei as a host-adapted pathogen

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Abstract

Pathogenic Shigella spp. are the leading cause of bacterial dysentery, with Shigella flexneri and Shigella sonnei accounting for around 90% of cases worldwide. Although S. flexneri causes most disease in low-income countries (following ingestion of contaminated food and/or water), S. sonnei predominates in wealthy countries and is mainly spread from person to person. Although both species contain a large virulence plasmid, pINV, that is essential for the organism to cause disease, little is known about its maintenance. Here, using a counterselectable marker within the virulence-encoding region of pINV, we show that the S. sonnei plasmid is less stable than that of S. flexneri, especially at environmental temperatures. GmvAT, a toxin–antitoxin system, is responsible for the difference in stability and is present in pINV from S. flexneri but absent in S. sonnei pINV. GmvT is an acetyltransferase toxin that inhibits protein translation. Loss of GmvAT and a second toxin–antitoxin system, CcdAB, from pINV reduces S. sonnei plasmid stability outside the host, reflecting the host-adapted lifestyle and person-to-person transmission of this species and differences in its epidemiology.

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Figure 1: Loss of virulence in S. sonnei is temperature-dependent and higher than in S. flexneri.
Figure 2: S. flexneri pINV has three functional TA systems.
Figure 3: S. flexneri pINV TA systems have temperature-dependent effects on plasmid maintenance.
Figure 4: GmvT blocks translation in an acetyl-CoA-dependent manner.
Figure 5: Absence of GmvAT and CcdAB in S. sonnei leads to increased pINV loss.
Figure 6: Insertion of CcdAB and GmvAT into wild-type S. sonnei stabilizes virulence at environmental temperatures.

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  • 14 July 2017

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Acknowledgements

The authors thank I. Blomfield for the gift of P1vir bacteriophage and pIB279 (sacB-neoR), W. Dias da Silveira for S. sonnei strain CS20 and K. Baker and N. Thomson for assistance with genomic analyses. The authors acknowledge the Kirkhouse Trust (Scottish charity no. 030508) for donation of laboratory equipment. This work was funded by Stopenterics EU grant no. 261472 and a Wellcome Trust Senior Investigator award to C.M.T.

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G.M. performed experiments and analysed data. G.M. and C.M.T. designed experiments, interpreted data and wrote the manuscript. C.M.T. secured funding.

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Correspondence to Christoph M. Tang.

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McVicker, G., Tang, C. Deletion of toxin–antitoxin systems in the evolution of Shigella sonnei as a host-adapted pathogen. Nat Microbiol 2, 16204 (2017). https://doi.org/10.1038/nmicrobiol.2016.204

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