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

Abstract

Pathogenic Shigella spp. are the leading cause of bacterial dysentery, with Shigella flexneri and Shigella sonnei accounting for around 90% of cases worldwide. While 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 hence the striking differences in its epidemiology