| 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
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Prokaryotes E. coli |
|
