title: The MazEF Toxin-Antitoxin System Alters the β-Lactam Susceptibility of Staphylococcus aureus.
abstract: Toxin-antitoxin (TA) systems are genetic elements of prokaryotes which encode a stable toxin and an unstable antitoxin that can counteract toxicity. TA systems residing on plasmids are often involved in episomal maintenance whereas those on chromosomes can have multiple functions. The opportunistic pathogen Staphylococcus aureus possesses at least four different families of TA systems but their physiological roles are elusive. The chromosomal mazEF system encodes the RNase toxin MazF and the antitoxin MazE. In the light of ambiguity regarding the cleavage activity, we here verify that MazF specifically targets UACAU sequences in S. aureus in vivo. In a native strain background and under non-stress conditions, cleavage was observed in the absence or presence of mazE. Transcripts of spa (staphylococcal protein A) and rsbW (anti-σB factor) were cut, but translational reporter fusions indicated that protein levels of the encoded products were unaffected. Despite a comparable growth rate as the wild-type, an S. aureus mazEF deletion mutant was more susceptible to β-lactam antibiotics, which suggests that further genes, putatively involved in the antibiotic stress response or cell wall synthesis or turnover, are controlled by this TA system.
authors.affiliation: Department of Microbial Genetics, Faculty of Science, Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen, Tübingen, Germany.
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Schuster
authors.affiliation: Department of Microbial Genetics, Faculty of Science, Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen, Tübingen, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Mechler
authors.affiliation: Department of Microbial Genetics, Faculty of Science, Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen, Tübingen, Germany.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Nolle
authors.affiliation: Cellular and Molecular Microbiology, IMIT, University of Tübingen, German Center for Infection Research (DZIF), partner site Tübingen, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Krismer
authors.affiliation: Department of Microbial Genetics, Faculty of Science, Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen, Tübingen, Germany.
authors.forename: Marc-Eric
authors.initials: ME
authors.lastname: Zelder
authors.affiliation: Department of Microbial Genetics, Faculty of Science, Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen, Tübingen, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Götz
authors.affiliation: Department of Microbial Genetics, Faculty of Science, Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen, Tübingen, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Bertram
mesh_terms: D000992:Antitoxins / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000235:genetics* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics / Q000472:pathogenicity*; D047090:beta-Lactams / Q000378:metabolism*
chemical_list: D000992:Antitoxins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004268:DNA-Binding Proteins; C540055:MazE protein, Staphylococcus aureus; D047090:beta-Lactams