RRC ID 35653
Author Tripathi A, Dewan PC, Siddique SA, Varadarajan R.
Title MazF-induced growth inhibition and persister generation in Escherichia coli.
Journal J Biol Chem
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.
Volume 289(7)
Pages 4191-205
Published 2014-2-14
DOI 10.1074/jbc.M113.510511
PII S0021-9258(20)44203-6
PMID 24375411
PMC PMC3924284
MeSH Amino Acid Substitution Anti-Bacterial Agents / pharmacology Catalytic Domain DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Endopeptidase Clp / genetics Endopeptidase Clp / metabolism* Endoribonucleases / genetics Endoribonucleases / metabolism* Escherichia coli K12 / genetics Escherichia coli K12 / growth & development* Escherichia coli Proteins / genetics Escherichia coli Proteins / metabolism* Mutation, Missense Protease La / genetics Protease La / metabolism* Rec A Recombinases / genetics Rec A Recombinases / metabolism* Stress, Physiological / drug effects Stress, Physiological / physiology*
IF 4.238
Times Cited 45
Prokaryotes E. coli