title: Molecular and functional profiling of the polyamine content in enteroinvasive E. coli : looking into the gap between commensal E. coli and harmful Shigella.
abstract: Polyamines are small molecules associated with a wide variety of physiological functions. Bacterial pathogens have developed subtle strategies to exploit polyamines or manipulate polyamine-related processes to optimize fitness within the host. During the transition from its innocuous E. coli ancestor, Shigella, the aetiological agent of bacillary dysentery, has undergone drastic genomic rearrangements affecting the polyamine profile. A pathoadaptation process involving the speG gene and the cad operon has led to spermidine accumulation and loss of cadaverine. While a higher spermidine content promotes the survival of Shigella within infected macrophages, the lack of cadaverine boosts the pathogenic potential of the bacterium in host tissues. Enteroinvasive E. coli (EIEC) display the same pathogenicity process as Shigella, but have a higher infectious dose and a higher metabolic activity. Pathoadaption events affecting the cad locus have occurred also in EIEC, silencing cadaverine production. Since EIEC are commonly regarded as evolutionary intermediates between E. coli and Shigella, we investigated on their polyamine profile in order to better understand which changes have occurred along the path to pathogenicity. By functional and molecular analyses carried out in EIEC strains belonging to different serotypes, we show that speG has been silenced in one strain only, favouring resistance to oxidative stress conditions and survival within macrophages. At the same time, we observe that the content of spermidine and putrescine, a relevant intermediate in the synthesis of spermidine, is higher in all strains as compared to E. coli. This may represent an evolutionary response to the lack of cadaverine. Indeed, restoring cadaverine synthesis decreases the expression of the speC gene, whose product affects putrescine production. In the light of these results, we discuss the possible impact of pathoadaptation events on the evolutionary emergence of a polyamine profile favouring to the pathogenic lifestyle of Shigella and EIEC.
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Biologia e Biotecnologie "C. Darwin", Sapienza Università di Roma, Roma, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Campilongo
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Biologia e Biotecnologie "C. Darwin", Sapienza Università di Roma, Roma, Italy; Dipartimento di Scienze, Università Roma Tre, Roma, Italy.
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Di Martino
authors.affiliation: Dipartimento di Biochimica, Sapienza Università di Roma, Roma, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Marcocci
authors.affiliation: Dipartimento di Biochimica, Sapienza Università di Roma, Roma, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Pietrangeli
authors.affiliation: Istituto Pasteur-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-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: Dipartimento di Scienze, Università Roma Tre, Roma, Italy.
authors.forename: Mariassunta
authors.initials: M
authors.lastname: Casalino
authors.affiliation: Dipartimento di Scienze Sperimentali e Cliniche, Università G. D'Annunzio, Chieti, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Nicoletti
authors.affiliation: Istituto di Biologia, Medicina Molecolare e NanoBiotecnologie, Consiglio Nazionale delle Ricerche, Roma, Italy.
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Micheli
authors.affiliation: Istituto Pasteur-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-Fondazione Cenci Bolognetti, Dipartimento di Biologia e Biotecnologie "C. Darwin", Sapienza Università di Roma, Roma, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Prosseda
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002103:Cadaverine / Q000096:biosynthesis; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D023061:Gene Order; D053858:Metabolic Networks and Pathways; D051379:Mice; D008969:Molecular Sequence Data; D009876:Operon; D018384:Oxidative Stress; D011073:Polyamines / Q000378:metabolism*; D012760:Shigella / Q000235:genetics* / Q000378:metabolism*; D013095:Spermidine / Q000096:biosynthesis
chemical_list: D001426:Bacterial Proteins; D011073:Polyamines; D002103:Cadaverine; D013095:Spermidine