title: Role of the SRRz/Rz1lambdoid lysis cassette in the pathoadaptive evolution of Shigella.
abstract: Shigella, the etiological agent of bacillary dysentery (shigellosis), is a highly adapted human pathogen. It evolved from an innocuous ancestor resembling the Escherichia coli strain by gain and loss of genes and functions. While the gain process concerns the acquisition of the genetic determinants of virulence, the loss is related to the adaptation of the genome to the new pathogenic status and occurs by pathoadaptive mutation of antivirulence genes. In this study, we highlight that the SRRz/Rz1lambdoid lysis cassette, even though stably adopted in E. coli K12 by virtue of its beneficial effect on cell physiology, has undergone a significant decay in Shigella. Moreover, we show the antivirulence nature of the SRRz/Rz1lysis cassette in Shigella. In fact, by restoring the SRRz/Rz1expression in this pathogen, we observe an increased release of peptidoglycan fragments, causing an unbalance in the fine control exerted by Shigella on host innate immunity and a mitigation of its virulence. This strongly affects the virulence of Shigella and allows to consider the loss of SRRz/Rz1lysis cassette as another pathoadaptive event in the life of Shigella.
authors.affiliation: Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Dipartimento di Biologia e Biotecnologie "C. Darwin", Sapienza Università di Roma, Roma, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Leuzzi
authors.affiliation: Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Dipartimento di Biologia e Biotecnologie "C. Darwin", Sapienza Università di Roma, Roma, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Grossi
authors.affiliation: Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Dipartimento di Biologia e Biotecnologie "C. Darwin", Sapienza Università di Roma, Roma, Italy.
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Di Martino
authors.affiliation: Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Dipartimento di Biologia e Biotecnologie "C. Darwin", Sapienza Università di Roma, Roma, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Pasqua
authors.affiliation: Istituto di Biologia e Patologia Molecolari, Consiglio Nazionale delle Ricerche, Roma, Italy.
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Micheli
authors.affiliation: Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Dipartimento di Biologia e Biotecnologie "C. Darwin", Sapienza Università di Roma, Roma, Italy.
authors.forename: Bianca
authors.initials: B
authors.lastname: Colonna
authors.affiliation: Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Dipartimento di Biologia e Biotecnologie "C. Darwin", Sapienza Università di Roma, Roma, Italy. Electronic address: gianni.prosseda@uniroma1.it.
authors.forename: Gianni
authors.initials: G
authors.lastname: Prosseda
mesh_terms: D000818:Animals; D003001:Cloning, Molecular; D053938:DNA Fragmentation; D004269:DNA, Bacterial / Q000235:genetics; D004405:Dysentery, Bacillary / Q000382:microbiology*; D004926:Escherichia coli / Q000235:genetics; D019143:Evolution, Molecular; D005798:Genes, Bacterial; D006367:HeLa Cells; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007915:Lepidoptera / Q000382:microbiology; D009154:Mutation; D009876:Operon / Q000235:genetics; D012760:Shigella / Q000235:genetics* / Q000472:pathogenicity; D014774:Virulence / Q000235:genetics*
chemical_list: D004269:DNA, Bacterial; D016209:Interleukin-8
keywords: Bacterial evolution; Bacterial-host interaction; Pathoadaptive mutation; Peptidoglycan; Shigella