Role of the SRRz/Rz1 lambdoid lysis cassette in the pathoadaptive evolution of Shigella

Shigella, the etiological agent of bacillary dysentery (shigellosis), is a highly adapted human pathogen. Itevolved from an innocuous ancestor resembling the Escherichia coli strain by gain and loss of genes andfunctions. While the gain process concerns the acquisition of the genetic determinants of virulence, theloss is related to the adaptation of the genome to the new pathogenic status and occurs by pathoadaptivemutation of antivirulence genes. In this study, we highlight that the SRRz/Rz1lambdoid lysis cassette, eventhough stably adopted in E. coli K12 by virtue of its beneficial effect on cell physiology, has undergone asignificant decay in Shigella. Moreover, we show the antivirulence nature of the SRRz/Rz1lysis cassette inShigella. In fact, by restoring the SRRz/Rz1expression in this pathogen, we observe an increased releaseof peptidoglycan fragments, causing an unbalance in the fine control exerted by Shigella on host innateimmunity and a mitigation of its virulence. This strongly affects the virulence of Shigella and allows toconsider the loss of SRRz/Rz1lysis cassette as another pathoadaptive event in the life of Shigella.