title: Functional interactions between coexisting toxin-antitoxin systems of the ccd family in Escherichia coli O157:H7.
abstract: Toxin-antitoxin (TA) systems are widely represented on mobile genetic elements as well as in bacterial chromosomes. TA systems encode a toxin and an antitoxin neutralizing it. We have characterized a homolog of the ccd TA system of the F plasmid (ccd(F)) located in the chromosomal backbone of the pathogenic O157:H7 Escherichia coli strain (ccd(O157)). The ccd(F) and the ccd(O157) systems coexist in O157:H7 isolates, as these pathogenic strains contain an F-related virulence plasmid carrying the ccd(F) system. We have shown that the chromosomal ccd(O157) system encodes functional toxin and antitoxin proteins that share properties with their plasmidic homologs: the CcdB(O157) toxin targets the DNA gyrase, and the CcdA(O157) antitoxin is degraded by the Lon protease. The ccd(O157) chromosomal system is expressed in its natural context, although promoter activity analyses revealed that its expression is weaker than that of ccd(F). ccd(O157) is unable to mediate postsegregational killing when cloned in an unstable plasmid, supporting the idea that chromosomal TA systems play a role(s) other than stabilization in bacterial physiology. Our cross-interaction experiments revealed that the chromosomal toxin is neutralized by the plasmidic antitoxin while the plasmidic toxin is not neutralized by the chromosomal antitoxin, whether expressed ectopically or from its natural context. Moreover, the ccd(F) system is able to mediate postsegregational killing in an E. coli strain harboring the ccd(O157) system in its chromosome. This shows that the plasmidic ccd(F) system is functional in the presence of its chromosomal counterpart.
authors.affiliation: Laboratoire de Génétique des Procaryotes, Institut de Biologie et Médecine Moléculaires, Université Libre de Bruxelles, 12 Rue des Professeurs Jeener et Brachet, 6041 Gosselies, Belgium.
authors.forename: Myriam
authors.initials: M
authors.lastname: Wilbaux
authors.forename: Natacha
authors.initials: N
authors.lastname: Mine
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Guérout
authors.forename: Didier
authors.initials: D
authors.lastname: Mazel
authors.forename: Laurence
authors.initials: L
authors.lastname: Van Melderen
mesh_terms: D000595:Amino Acid Sequence; D000992:Antitoxins / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002876:Chromosomes, Bacterial / Q000235:genetics; D017931:DNA Primers; D019453:Escherichia coli O157 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D010957:Plasmids; D016133:Polymerase Chain Reaction
chemical_list: D000992:Antitoxins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; C068355:CcdA protein, Bacteria; C068356:CcdB protein, Plasmid F; D017931:DNA Primers; D029968:Escherichia coli Proteins