title: MazF-induced growth inhibition and persister generation in Escherichia coli.
abstract: Toxin-antitoxin systems are ubiquitous in nature and present on the chromosomes of both bacteria and archaea. MazEF is a type II toxin-antitoxin system present on the chromosome of Escherichia coli and other bacteria. Whether MazEF is involved in programmed cell death or reversible growth inhibition and bacterial persistence is a matter of debate. In the present work the role of MazF in bacterial physiology was studied by using an inactive, active-site mutant of MazF, E24A, to activate WT MazF expression from its own promoter. The ectopic expression of E24A MazF in a strain containing WT mazEF resulted in reversible growth arrest. Normal growth resumed on inhibiting the expression of E24A MazF. MazF-mediated growth arrest resulted in an increase in survival of bacterial cells during antibiotic stress. This was studied by activation of mazEF either by overexpression of an inactive, active-site mutant or pre-exposure to a sublethal dose of antibiotic. The MazF-mediated persistence phenotype was found to be independent of RecA and dependent on the presence of the ClpP and Lon proteases. This study confirms the role of MazEF in reversible growth inhibition and persistence.
authors.affiliation: From the Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India and.
authors.forename: Arti
authors.initials: A
authors.lastname: Tripathi
authors.forename: Pooja C
authors.initials: PC
authors.lastname: Dewan
authors.forename: Shahbaz
authors.initials: S
authors.lastname: Ahmed
authors.forename: Raghavan
authors.initials: R
authors.lastname: Varadarajan
mesh_terms: D019943:Amino Acid Substitution; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D020134:Catalytic Domain; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D049071:Endopeptidase Clp / Q000235:genetics / Q000378:metabolism*; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D048168:Escherichia coli K12 / Q000235:genetics / Q000254:growth & development*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D020125:Mutation, Missense; D049070:Protease La / Q000235:genetics / Q000378:metabolism*; D011938:Rec A Recombinases / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C422955:MazF protein, E coli; D011938:Rec A Recombinases; D004722:Endoribonucleases; C483567:Lon protein, E coli; D049070:Protease La; D049071:Endopeptidase Clp
keywords: Antibiotic Tolerance; Antibiotics; Bacteriostasis; Cell Death; Inactive, Active-site Mutant; Mutant; Protein Degradation; Protein Synthesis; Toxin-Antitoxin