title: The axe-txe complex of Enterococcus faecium presents a multilayered mode of toxin-antitoxin gene expression regulation.
abstract: Multidrug-resistant variants of human pathogens from the genus Enterococcus represent a significant health threat as leading agents of nosocomial infections. The easy acquisition of plasmid-borne genes is intimately involved in the spread of antibiotic resistance in enterococci. Toxin-antitoxin (TA) systems play a major role in both maintenance of mobile genetic elements that specify antibiotic resistance, and in bacterial persistence and virulence. Expression of toxin and antitoxin genes must be in balance as inappropriate levels of toxin can be dangerous to the host. The controlled production of toxin and antitoxin is usually achieved by transcriptional autoregulation of TA operons. One of the most prevalent TA modules in enterococcal species is axe-txe which is detected in a majority of clinical isolates. Here, we demonstrate that the axe-txe cassette presents a complex pattern of gene expression regulation. Axe-Txe cooperatively autorepress expression from a major promoter upstream of the cassette. However, an internal promoter that drives the production of a newly discovered transcript from within axe gene combined with a possible modulation in mRNA stability play important roles in the modulation of Axe:Txe ratio to ensure controlled release of the toxin.
authors.affiliation: Department of Molecular Biology, University of Gdańsk, Gdańsk, Poland.
authors.forename: Lidia
authors.initials: L
authors.lastname: Boss
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Labudda
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Węgrzyn
authors.forename: Finbarr
authors.initials: F
authors.lastname: Hayes
authors.forename: Barbara
authors.initials: B
authors.lastname: Kędzierska
mesh_terms: D000992:Antitoxins / Q000235:genetics*; D001427:Bacterial Toxins / Q000494:pharmacology*; D001483:Base Sequence; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D016984:Enterococcus faecium / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D005798:Genes, Bacterial; D009875:Operator Regions, Genetic; D010957:Plasmids; D011401:Promoter Regions, Genetic
chemical_list: D000992:Antitoxins; D001427:Bacterial Toxins; D017931:DNA Primers
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