Gene Symbol: mazF
Description: mRNA interferase toxin, antitoxin is MazE
Alias: ECK2776, JW2753, chpA, chpAK
Species: Escherichia coli str. K-12 substr. MG1655

Top Publications

  1. Muñoz Gómez A, Santos Sierra S, Berzal Herranz A, Lemonnier M, Díaz Orejas R. Insights into the specificity of RNA cleavage by the Escherichia coli MazF toxin. FEBS Lett. 2004;567:316-20 pubmed
    The mazEF (chpA) toxin-antitoxin system of Escherichia coli is involved in the cell response to nutritional and antibiotic stresses as well as in bacterial-programmed cell death...
  2. Godoy V, Jarosz D, Walker F, Simmons L, Walker G. Y-family DNA polymerases respond to DNA damage-independent inhibition of replication fork progression. EMBO J. 2006;25:868-79 pubmed
    ..This novel function reveals a role for Y-family polymerases in enhancing cell survival under conditions of nucleotide starvation, in addition to their established functions in response to DNA damage. ..
  3. Gerdes K. Toxin-antitoxin modules may regulate synthesis of macromolecules during nutritional stress. J Bacteriol. 2000;182:561-72 pubmed
  4. Kolodkin Gal I, Verdiger R, Shlosberg Fedida A, Engelberg Kulka H. A differential effect of E. coli toxin-antitoxin systems on cell death in liquid media and biofilm formation. PLoS ONE. 2009;4:e6785 pubmed publisher
    ..Cell death governed by mazEF and dinJ-YafQ seems to participate in biofilm formation through a novel mechanism. ..
  5. Kolodkin Gal I, Engelberg Kulka H. Induction of Escherichia coli chromosomal mazEF by stressful conditions causes an irreversible loss of viability. J Bacteriol. 2006;188:3420-3 pubmed
    ..These results further support our previous conclusion that E. coli mazEF mediation of cell death is not a passive process, but an active and genetically "programmed" death response. ..
  6. Mittenhuber G. Occurrence of mazEF-like antitoxin/toxin systems in bacteria. J Mol Microbiol Biotechnol. 1999;1:295-302 pubmed
    ..A study on the sigmaB operon of Staphylococcus aureus showed that the mazF gene of this organism is cotranscribed with the sigmaB operon in response to heat shock, providing the first ..
  7. Sat B, Hazan R, Fisher T, Khaner H, Glaser G, Engelberg Kulka H. Programmed cell death in Escherichia coli: some antibiotics can trigger mazEF lethality. J Bacteriol. 2001;183:2041-5 pubmed
    ..We have reported on the E. coli mazEF system, a regulatable addiction module located on the bacterial chromosome. MazF is a stable toxin and MazE is a labile antitoxin. Here we show that cell death mediated by the E...
  8. Nariya H, Inouye M. MazF, an mRNA interferase, mediates programmed cell death during multicellular Myxococcus development. Cell. 2008;132:55-66 pubmed publisher
    ..In the E. coli MazE-MazF system, MazF toxin functions as an mRNA interferase cleaving mRNAs at ACA sequences to inhibit protein synthesis ..
  9. Belitsky M, Avshalom H, Erental A, Yelin I, Kumar S, London N, et al. The Escherichia coli extracellular death factor EDF induces the endoribonucleolytic activities of the toxins MazF and ChpBK. Mol Cell. 2011;41:625-35 pubmed publisher
    ..E. coli toxin MazF is a sequence-specific endoribonuclease cleaving single-stranded mRNAs at ACA sequences. E...

More Information


  1. Kamada K, Hanaoka F, Burley S. Crystal structure of the MazE/MazF complex: molecular bases of antidote-toxin recognition. Mol Cell. 2003;11:875-84 pubmed
    A structure of the Escherichia coli chromosomal MazE/MazF addiction module has been determined at 1.7 A resolution. Addiction modules consist of stable toxin and unstable antidote proteins that govern bacterial cell death...
  2. Kolodkin Gal I, Engelberg Kulka H. The extracellular death factor: physiological and genetic factors influencing its production and response in Escherichia coli. J Bacteriol. 2008;190:3169-75 pubmed publisher
    ..The most studied of these modules is Escherichia coli mazEF, in which mazF encodes a stable toxin, MazF, and mazE encodes a labile antitoxin, MazE, which prevents the lethal effect of MazF...
  3. Amitai S, Kolodkin Gal I, Hananya Meltabashi M, Sacher A, Engelberg Kulka H. Escherichia coli MazF leads to the simultaneous selective synthesis of both "death proteins" and "survival proteins". PLoS Genet. 2009;5:e1000390 pubmed publisher
    The Escherichia coli mazEF module is one of the most thoroughly studied toxin-antitoxin systems. mazF encodes a stable toxin, MazF, and mazE encodes a labile antitoxin, MazE, which prevents the lethal effect of MazF...
  4. Marianovsky I, Aizenman E, Engelberg Kulka H, Glaser G. The regulation of the Escherichia coli mazEF promoter involves an unusual alternating palindrome. J Biol Chem. 2001;276:5975-84 pubmed
    ..This module specifies for the toxic stable protein MazF and the labile antitoxic protein MazE...
  5. Inouye M. The discovery of mRNA interferases: implication in bacterial physiology and application to biotechnology. J Cell Physiol. 2006;209:670-6 pubmed
    ..coli contains so many toxin genes and what are their roles in bacterial physiology. Among these, MazF has been shown to be a sequence-specific endoribonuclease, which cleaves mRNAs at ACA sequences to completely ..
  6. Amitai S, Yassin Y, Engelberg Kulka H. MazF-mediated cell death in Escherichia coli: a point of no return. J Bacteriol. 2004;186:8295-300 pubmed
    ..coli. mazF specifies a stable toxin, and mazE specifies a labile antitoxin...
  7. Engelberg Kulka H, Hazan R, Amitai S. mazEF: a chromosomal toxin-antitoxin module that triggers programmed cell death in bacteria. J Cell Sci. 2005;118:4327-32 pubmed
    ..b>mazF specifies for a stable toxin, MazF, and mazE specifies for a labile antitoxin, MazE, that antagonizes MazF...
  8. Metzger S, Dror I, Aizenman E, Schreiber G, Toone M, Friesen J, et al. The nucleotide sequence and characterization of the relA gene of Escherichia coli. J Biol Chem. 1988;263:15699-704 pubmed
    ..coli chromosome. Genomic Southern blot analyses verify that the relA regions cloned and subjected to nucleotide sequence analysis correspond to homologous regions on the E. coli chromosome...
  9. Hazan R, Sat B, Engelberg Kulka H. Escherichia coli mazEF-mediated cell death is triggered by various stressful conditions. J Bacteriol. 2004;186:3663-9 pubmed
    ..We also show that this process takes place only during logarithmic growth and requires an intact relA gene. ..
  10. Zhang Y, Zhang J, Hoeflich K, Ikura M, Qing G, Inouye M. MazF cleaves cellular mRNAs specifically at ACA to block protein synthesis in Escherichia coli. Mol Cell. 2003;12:913-23 pubmed
    ..Here, we demonstrate that MazF toxin encoded by "mazEF addiction module" is a sequence-specific (ACA) endoribonuclease functional only for single-..
  11. Hazan R, Sat B, Reches M, Engelberg Kulka H. Postsegregational killing mediated by the P1 phage "addiction module" phd-doc requires the Escherichia coli programmed cell death system mazEF. J Bacteriol. 2001;183:2046-50 pubmed
    ..coli is inhibited. Based on our findings, we suggest the existence of a coupling between the phd-doc and mazEF systems. ..
  12. Engelberg Kulka H, Reches M, Narasimhan S, Schoulaker Schwarz R, Klemes Y, Aizenman E, et al. rexB of bacteriophage lambda is an anti-cell death gene. Proc Natl Acad Sci U S A. 1998;95:15481-6 pubmed
    ..Thus, the rex operon may be considered as the "survival operon" of phage lambda. ..
  13. Aizenman E, Engelberg Kulka H, Glaser G. An Escherichia coli chromosomal "addiction module" regulated by guanosine [corrected] 3',5'-bispyrophosphate: a model for programmed bacterial cell death. Proc Natl Acad Sci U S A. 1996;93:6059-63 pubmed
    ..Here we show that the chromosomal genes mazE and mazF, located in the Escherichia coli rel operon, have all of the properties required for an addiction module...
  14. Christensen S, Pedersen K, Hansen F, Gerdes K. Toxin-antitoxin loci as stress-response-elements: ChpAK/MazF and ChpBK cleave translated RNAs and are counteracted by tmRNA. J Mol Biol. 2003;332:809-19 pubmed
    ..However, we found recently that ChpAK (MazF) does not confer cell killing but rather, induces a bacteriostatic condition from which the cells could be ..
  15. Kolodkin Gal I, Sat B, Keshet A, Engelberg Kulka H. The communication factor EDF and the toxin-antitoxin module mazEF determine the mode of action of antibiotics. PLoS Biol. 2008;6:e319 pubmed publisher
    ..found that antibiotics of both groups caused: (i) mazEF-mediated cell death, and (ii) the production of ROS through MazF action...
  16. Baik S, Inoue K, Ouyang M, Inouye M. Significant bias against the ACA triplet in the tmRNA sequence of Escherichia coli K-12. J Bacteriol. 2009;191:6157-66 pubmed publisher
    The toxin MazF in Escherichia coli cleaves single-stranded RNAs specifically at ACA sequences. MazF overexpression virtually eliminates all cellular mRNAs to completely block protein synthesis...
  17. Sat B, Reches M, Engelberg Kulka H. The Escherichia coli mazEF suicide module mediates thymineless death. J Bacteriol. 2003;185:1803-7 pubmed
    ..coli mazEF system, a regulatable chromosomal suicide module that can be triggered by various stress conditions. MazF is a stable toxin, and MazE is an unstable antitoxin...
  18. Suzuki M, Zhang J, Liu M, Woychik N, Inouye M. Single protein production in living cells facilitated by an mRNA interferase. Mol Cell. 2005;18:253-61 pubmed
    We designed a single-protein production (SPP) system in living E. coli cells that exploits the unique properties of MazF, a bacterial toxin that is an ssRNA- and ACA-specific endoribonuclease...
  19. Gross M, Marianovsky I, Glaser G. MazG -- a regulator of programmed cell death in Escherichia coli. Mol Microbiol. 2006;59:590-601 pubmed
    ..It consists of a pair of genes encoding a stable toxin, MazF, and MazE, a labile antitoxin interacting with MazF to form a complex...
  20. Kolodkin Gal I, Hazan R, Gaathon A, Carmeli S, Engelberg Kulka H. A linear pentapeptide is a quorum-sensing factor required for mazEF-mediated cell death in Escherichia coli. Science. 2007;318:652-5 pubmed
    ..Structural analysis revealed that EDF is a linear pentapeptide, Asn-Asn-Trp-Asn-Asn. Each of the five amino acids of EDF is important for its activity. ..
  21. Vesper O, Amitai S, Belitsky M, Byrgazov K, Kaberdina A, Engelberg Kulka H, et al. Selective translation of leaderless mRNAs by specialized ribosomes generated by MazF in Escherichia coli. Cell. 2011;147:147-57 pubmed publisher
    Escherichia coli (E. coli) mazEF is a stress-induced toxin-antitoxin (TA) module. The toxin MazF is an endoribonuclease that cleaves single-stranded mRNAs at ACA sequences...
  22. Engelberg Kulka H, Amitai S, Kolodkin Gal I, Hazan R. Bacterial programmed cell death and multicellular behavior in bacteria. PLoS Genet. 2006;2:e135 pubmed
    ..We relate these two bacterial PCD systems to the ways in which bacterial populations resemble multicellular organisms. ..
  23. Masuda Y, Miyakawa K, Nishimura Y, Ohtsubo E. chpA and chpB, Escherichia coli chromosomal homologs of the pem locus responsible for stable maintenance of plasmid R100. J Bacteriol. 1993;175:6850-6 pubmed
    ..The pem locus homolog at 60 min was named chpA and consists of two genes, chpAI and chpAK; the other, at 100 min, was named chpB and consists of two genes, chpBI and chpBK...
  24. de la Cueva M ndez G. Distressing bacteria: structure of a prokaryotic detox program. Mol Cell. 2003;11:848-50 pubmed
    b>MazF and MazE are components of a chromosomal toxin-antitoxin system of Escherichia coli. In this issue of Molecular Cell, Kamada et al...
  25. Lah J, Marianovsky I, Glaser G, Engelberg Kulka H, Kinne J, Wyns L, et al. Recognition of the intrinsically flexible addiction antidote MazE by a dromedary single domain antibody fragment. Structure, thermodynamics of binding, stability, and influence on interactions with DNA. J Biol Chem. 2003;278:14101-11 pubmed publisher
    ..It encodes the toxic and long-lived MazF and the labile antidote MazE. The denaturation of MazE is a two-state reversible dimer-monomer transition...
  26. Zhang Y, Zhang J, Hara H, Kato I, Inouye M. Insights into the mRNA cleavage mechanism by MazF, an mRNA interferase. J Biol Chem. 2005;280:3143-50 pubmed
    b>MazF is an Escherichia coli toxin that is highly conserved among the prokaryotes and plays an important role in growth regulation. When MazF is induced, protein synthesis is effectively inhibited...
  27. Pandey D, Gerdes K. Toxin-antitoxin loci are highly abundant in free-living but lost from host-associated prokaryotes. Nucleic Acids Res. 2005;33:966-76 pubmed publisher
    ..RelE and MazF toxins are regulators of translation that cleave mRNA and function, in interplay with tmRNA, in quality control of ..
  28. Pedersen K, Christensen S, Gerdes K. Rapid induction and reversal of a bacteriostatic condition by controlled expression of toxins and antitoxins. Mol Microbiol. 2002;45:501-10 pubmed
    RelE and ChpAK (MazF) toxins of Escherichia coli have previously been described as proteins that mediate efficient cell killing...
  29. Rosenberg S. Life, death, differentiation, and the multicellularity of bacteria. PLoS Genet. 2009;5:e1000418 pubmed publisher
  30. Alawneh A, Qi D, Yonesaki T, Otsuka Y. An ADP-ribosyltransferase Alt of bacteriophage T4 negatively regulates the Escherichia coli MazF toxin of a toxin-antitoxin module. Mol Microbiol. 2016;99:188-98 pubmed publisher
    ..Here, we describe a novel regulatory mechanism for a toxin of Escherichia coli TA systems. The MazF toxin of MazE-MazF, which is one of the best characterized type II TA systems, was modified immediately after ..
  31. Lewis K. Multidrug tolerance of biofilms and persister cells. Curr Top Microbiol Immunol. 2008;322:107-31 pubmed
    ..Ectopic expression of RelE, MazF, and HipA toxins produced multidrug tolerant cells...
  32. Mao L, Vaiphei S, Shimazu T, Schneider W, Tang Y, Mani R, et al. The E. coli single protein production system for production and structural analysis of membrane proteins. J Struct Funct Genomics. 2010;11:81-4 pubmed publisher
    ..Here we address some of the major bottlenecks in the structural studies of membrane proteins and discuss the ability of the new technology, the Single-Protein Production system, to help solve these bottlenecks. ..
  33. Cheng W, Hardwick J. A quorum on bacterial programmed cell death. Mol Cell. 2007;28:515-7 pubmed
    ..2007) reported a novel programmed cell death mechanism for Escherichia coli that occurs during cellular overcrowding via the release of a fratricidal pentapeptide derived from the metabolic enzyme glucose-6-phosphate dehydrogenase. ..
  34. Chono H, Saito N, Tsuda H, Shibata H, Ageyama N, Terao K, et al. In vivo safety and persistence of endoribonuclease gene-transduced CD4+ T cells in cynomolgus macaques for HIV-1 gene therapy model. PLoS ONE. 2011;6:e23585 pubmed publisher
    b>MazF is an endoribonuclease encoded by Escherichia coli that specifically cleaves the ACA sequence of mRNA. In our previous report, conditional expression of MazF in the HIV-1 LTR rendered CD4+ T lymphocytes resistant to HIV-1 replication...
  35. Santos Sierra S, Giraldo R, Diaz Orejas R. Functional interactions between homologous conditional killer systems of plasmid and chromosomal origin. FEMS Microbiol Lett. 1997;152:51-6 pubmed
    ..conditional killer systems of plasmid and chromosomal origin, respectively, encoding a killer protein (Kid and ChpAK) and an antidote (Kis and ChpAI). Here it is shown that these systems can functionally interact...
  36. Tsilibaris V, Maenhaut Michel G, Mine N, Van Melderen L. What is the benefit to Escherichia coli of having multiple toxin-antitoxin systems in its genome?. J Bacteriol. 2007;189:6101-8 pubmed
    ..This casts a doubt on whether TA systems significantly influence bacterial fitness and competitiveness during non-steady-state growth conditions. ..
  37. Engelberg Kulka H, Yelin I, Kolodkin Gal I. Activation of a built-in bacterial programmed cell death system as a novel mechanism of action of some antibiotics. Commun Integr Biol. 2009;2:211-2 pubmed
    ..In this Addendum article we present a model of how the presence of some antibiotics may result in this novel downstream pathway. ..
  38. Christensen Dalsgaard M, Overgaard M, Winther K, Gerdes K. RNA decay by messenger RNA interferases. Methods Enzymol. 2008;447:521-35 pubmed publisher
    ..In particular, we describe a set of plasmid vectors useful for the detailed analysis of cleavage sites in model mRNAs. ..
  39. Cruzeiro Silva C, Albernaz F, Valente A, Almeida F. In-Cell NMR spectroscopy: inhibition of autologous protein expression reduces Escherichia coli lysis. Cell Biochem Biophys. 2006;44:497-502 pubmed
    ..coli. We suggest that rifampicin is acting in the programmed cell death gene system MazEF, which is triggered by stress conditions and ultimately leads to cell lysis. ..
  40. Erental A, Sharon I, Engelberg Kulka H. Two programmed cell death systems in Escherichia coli: an apoptotic-like death is inhibited by the mazEF-mediated death pathway. PLoS Biol. 2012;10:e1001281 pubmed publisher
    ..The E. coli mazEF module is one of the most thoroughly studied toxin-antitoxin systems. mazF encodes a stable toxin, MazF, and mazE encodes a labile antitoxin, MazE, which prevents the lethal effect of MazF...
  41. Ramisetty B, Raj S, Ghosh D. Escherichia coli MazEF toxin-antitoxin system does not mediate programmed cell death. J Basic Microbiol. 2016;56:1398-1402 pubmed publisher
    ..We could not reproduce mazEF mediated PCD which emphasizes the need for skeptic approach to the PCD hypothesis. ..
  42. Zorzini V, Mernik A, Lah J, Sterckx Y, De Jonge N, Garcia Pino A, et al. Substrate Recognition and Activity Regulation of the Escherichia coli mRNA Endonuclease MazF. J Biol Chem. 2016;291:10950-60 pubmed publisher
    Escherichia coli MazF (EcMazF) is the archetype of a large family of ribonucleases involved in bacterial stress response...
  43. Yamaguchi Y, Inouye M. mRNA interferases, sequence-specific endoribonucleases from the toxin-antitoxin systems. Prog Mol Biol Transl Sci. 2009;85:467-500 pubmed publisher
    ..One such toxin, MazF, is an ACA-specific endoribonuclease, termed "mRNA interferase."E...
  44. Christensen Dalsgaard M, Gerdes K. Translation affects YoeB and MazF messenger RNA interferase activities by different mechanisms. Nucleic Acids Res. 2008;36:6472-81 pubmed publisher
    ..In contrast, site-specific mRNA cleavage by MazF occurred independently of translation...
  45. Li G, Zhang Y, Chan M, Mal T, Hoeflich K, Inouye M, et al. Characterization of dual substrate binding sites in the homodimeric structure of Escherichia coli mRNA interferase MazF. J Mol Biol. 2006;357:139-50 pubmed
    b>MazF and MazE constitute a so-called addiction module that is critical for bacterial growth arrest and eventual cell death in response to stress...
  46. Kolter R. Microbiology. Deadly priming. Science. 2007;318:578-9 pubmed
  47. Wang N, Hergenrother P. A continuous fluorometric assay for the assessment of MazF ribonuclease activity. Anal Biochem. 2007;371:173-83 pubmed
    ..The MazF toxin protein is known to be a ribonuclease...
  48. Suzuki M, Mao L, Inouye M. Single protein production (SPP) system in Escherichia coli. Nat Protoc. 2007;2:1802-10 pubmed
    ..Induction of MazF, an mRNA interferase that cleaves RNA at ACA nucleotide sequences, results in complete cell growth arrest...
  49. Temmel H, Muller C, Sauert M, Vesper O, Reiss A, Popow J, et al. The RNA ligase RtcB reverses MazF-induced ribosome heterogeneity in Escherichia coli. Nucleic Acids Res. 2017;45:4708-4721 pubmed publisher
    When Escherichia coli encounters stress, the endoribonuclease MazF initiates a post-transcriptional response that results in the reprogramming of protein synthesis...
  50. Kolodkin Gal I, Engelberg Kulka H. The stationary-phase sigma factor sigma(S) is responsible for the resistance of Escherichia coli stationary-phase cells to mazEF-mediated cell death. J Bacteriol. 2009;191:3177-82 pubmed publisher
    ..Deletion of rpoS, the gene encoding sigma(S) from the bacterial chromosome, permitted mazEF-mediated cell death during stationary growth phase. ..
  51. Tripathi A, Dewan P, Siddique S, Varadarajan R. MazF-induced growth inhibition and persister generation in Escherichia coli. J Biol Chem. 2014;289:4191-205 pubmed publisher
    ..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 ..
  52. Zhang J, Zhang Y, Inouye M. Characterization of the interactions within the mazEF addiction module of Escherichia coli. J Biol Chem. 2003;278:32300-6 pubmed publisher
    ..The mazEF system is known as an addiction module located on the Escherichia coli chromosome. MazF is a stable toxin, and MazE is a labile antitoxin interacting with MazF to form a complex...
  53. Zhang X, Yan X, Cui Z, Hong Q, Li S. mazF, a novel counter-selectable marker for unmarked chromosomal manipulation in Bacillus subtilis. Nucleic Acids Res. 2006;34:e71 pubmed
    ..Our new approach employed the Escherichia coli toxin gene mazF as a counter-selectable marker...
  54. Hazan R, Engelberg Kulka H. Escherichia coli mazEF-mediated cell death as a defense mechanism that inhibits the spread of phage P1. Mol Genet Genomics. 2004;272:227-34 pubmed
    The Escherichia coli gene pair mazEF is a regulatable chromosomal toxin-antitoxin module: mazF encodes a stable toxin and mazE encodes for a labile antitoxin that overcomes the lethal effect of MazF...
  55. Fico S, Mahillon J. TasA-tasB, a new putative toxin-antitoxin (TA) system from Bacillus thuringiensis pGI1 plasmid is a widely distributed composite mazE-doc TA system. BMC Genomics. 2006;7:259 pubmed
    ..Moreover, the association between TasA antitoxin with toxins other than TasB (and vice versa) revealed the composite and modular nature of bacterial TA systems. ..