title: Axe-Txe, a broad-spectrum proteic toxin-antitoxin system specified by a multidrug-resistant, clinical isolate of Enterococcus faecium.
abstract: Enterococcal species of bacteria are now acknowledged as leading causes of bacteraemia and other serious nosocomial infections. However, surprisingly little is known about the molecular mechanisms that promote the segregational stability of antibiotic resistance and other plasmids in these bacteria. Plasmid pRUM (24 873 bp) is a multidrug resistance plasmid identified in a clinical isolate of Enterococcus faecium. A novel proteic-based toxin-antitoxin cassette identified on pRUM was demonstrated to be a functional segregational stability module in both its native host and evolutionarily diverse bacterial species. Induced expression of the toxin protein (Txe) of this system resulted in growth inhibition in Escherichia coli. The toxic effect of Txe was alleviated by co-expression of the antitoxin protein, Axe. Homologues of the axe and txe genes are present in the genomes of a diversity of Eubacteria. These homologues (yefM-yoeB) present in the E. coli chromosome function as a toxin-antitoxin mechanism, although the Axe and YefM antitoxin components demonstrate specificity for their cognate toxin proteins in vivo. Axe-Txe is one of the first functional proteic toxin-antitoxin systems to be accurately described for Gram-positive bacteria.
authors.affiliation: Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology (UMIST), PO Box 88, Manchester M60 1QD, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Grady
authors.forename: Finbarr
authors.initials: F
authors.lastname: Hayes
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D002701:Chloramphenicol / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D016984:Enterococcus faecium / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D004917:Erythromycin / Q000494:pharmacology; D029968:Escherichia coli Proteins / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D005810:Multigene Family; D016366:Open Reading Frames; D010802:Phylogeny; D011815:R Factors / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013307:Streptomycin / Q000494:pharmacology; D013309:Streptothricins / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D011993:Recombinant Fusion Proteins; D013309:Streptothricins; D004917:Erythromycin; D002701:Chloramphenicol; D013307:Streptomycin