title: Regulatory crosstalk between type I and type II toxin-antitoxin systems in the human pathogen Enterococcus faecalis.
abstract: We discovered a chromosomal locus containing 2 toxin-antitoxin modules (TAs) with an antisense transcriptional organization in the E. faecalis clinical isolate V583. These TAs are homologous to the type I txpA-ratA system and the type II mazEF, respectively. We have shown that the putative MazF is toxic for E. coli and triggers RNA degradation, and its cognate antitoxin MazE counteracts toxicity. The second module, adjacent to mazEF, expresses a toxin predicted to belong to the TxpA type I family found in Firmicutes, and the antisense RNA antidote, RatA. Genomic analysis indicates that the cis-association of mazEF and txpA-ratA modules has been favored during evolution, suggesting a selective advantage for this TA organization in the E. faecalis species. We showed regulatory interplays between the 2 modules, involving transcription control and RNA stability. Remarkably, our data reveal that MazE and MazEF have a dual transcriptional activity: they act as autorepressors and activate ratA transcription, most likely in a direct manner. RatA controls txpA RNA levels through stability. Our data suggest a pivotal role of MazEF in the coordinated expression of mazEF and txpA-ratA modules in V583. To our knowledge, this is the first report describing a crosstalk between type I and II TAs.
authors: a INRA UMR1319 Micalis ; Jouy-en-Josas , France.|b AgroParisTech, UMR Micalis ; Jouy-en-Josas , France.
authors: Françoise
authors: F
authors: Wessner
authors: a INRA UMR1319 Micalis ; Jouy-en-Josas , France.|b AgroParisTech, UMR Micalis ; Jouy-en-Josas , France.
authors: Caroline
authors: C
authors: Lacoux
authors: c Université Libre de Bruxelles, Faculté des Sciences, Institut de Biologie et Médecine Moléculaire ; Gosselies , Belgium.
authors: Nathalie
authors: N
authors: Goeders
authors: a INRA UMR1319 Micalis ; Jouy-en-Josas , France.|b AgroParisTech, UMR Micalis ; Jouy-en-Josas , France.
authors: Aymeric
authors: A
authors: Fouquier d'Hérouel
authors: a INRA UMR1319 Micalis ; Jouy-en-Josas , France.|b AgroParisTech, UMR Micalis ; Jouy-en-Josas , France.
authors: Renata
authors: R
authors: Matos
authors: a INRA UMR1319 Micalis ; Jouy-en-Josas , France.|b AgroParisTech, UMR Micalis ; Jouy-en-Josas , France.
authors: Pascale
authors: P
authors: Serror
authors: c Université Libre de Bruxelles, Faculté des Sciences, Institut de Biologie et Médecine Moléculaire ; Gosselies , Belgium.
authors: Laurence
authors: L
authors: Van Melderen
authors: a INRA UMR1319 Micalis ; Jouy-en-Josas , France.|b AgroParisTech, UMR Micalis ; Jouy-en-Josas , France.
authors: Francis
authors: F
authors: Repoila
mesh_terms: D000595:Amino Acid Sequence; D000992:Antitoxins / Q000235:genetics*; D001427:Bacterial Toxins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004722:Endoribonucleases / Q000235:genetics; D013293:Enterococcus faecalis / Q000235:genetics* / Q000472:pathogenicity; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D020871:RNA Stability / Q000235:genetics; D016372:RNA, Antisense / Q000235:genetics*
chemical_list: D000992:Antitoxins; D001427:Bacterial Toxins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C422954:MazE protein, E coli; C422955:MazF protein, E coli; D016372:RNA, Antisense; C558779:RatA protein, E coli; D004722:Endoribonucleases
keywords: Enterococcus faecalis; RNA stability; antisense RNAs; toxin-antitoxin systems; transcription activation