Prokaryotic toxin-antitoxin stress response loci

Nature Reviews Microbiology

Volumn 3, Issue 5, 2005, Pages 371-382

  Gerdes, Kenn ^a   Christensen, Susanne K ^a   Løbner Olesen, Anders ^b  

^a UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

^b ROSKILDE UNIVERSITY   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

ANTITOXIN; MESSENGER RNA; NUCLEOTIDE; TOXIN;

APOPTOSIS; BACTERIAL CHROMOSOME; CODON; DATA BASE; GENE CASSETTE; GENE LOCUS; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; NUTRITION; PLASMID; PRIORITY JOURNAL; PROKARYOTE; REVIEW; RIBOSOME; RNA CLEAVAGE; STRESS;

ANTITOXINS; APOPTOSIS; BACTERIA; BACTERIAL TOXINS; CHROMOSOME MAPPING; CHROMOSOMES, BACTERIAL; MYCOBACTERIUM TUBERCULOSIS; OPERON; PLASMIDS; RNA, MESSENGER;

EID: 17844370503     PISSN: 17401526     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrmicro1147     Document Type: Review

References (134)

1. Cashel, M., Gentry, D., Hernandez, V. J. & Vinella, D. in Escherichia coli and Salmonella (ed. F. C. Neidthardt) 1458-1496 (ASM, Washington DC, 1996).
2. Murray, K. D. & Bremer, H. Control of spoT-dependent ppGpp synthesis and degradation in Escherichia coli. J. Mol. Biol. 259, 41-57 (1996).
3. Chatterji, D. & Kumar, O. A. Revisiting the stringent response, ppGpp and starvation signaling. Curr. Opin. Microbiol. 4, 160-165 (2001).
4. Barker, M. M., Gaal, T. & Gourse, R. L. Mechanism of regulation of transcription initiation by ppGpp. II. Models for positive control based on properties of RNAP mutants and competition for RNAP. J. Mol. Biol. 305, 689-702 (2001).
5. Barker, M. M., Gaal, T., Josaitis, C. A. & Gourse, R. L. Mechanism of regulation of transcription initiation by ppGpp. I. Effects of ppGpp on transcription initiation in vivo and in vitro. J. Mol. Biol. 305, 673-688 (2001).
6. Perederina, A. et al. Regulation through the secondary channel - structural framework for ppGpp-DksA synergism during transcription. Cell 118, 297-309 (2004).
7. Paul, B. J. et al. DksA: a critical component of the transcription initiation machinery that potentiates the regulation of rRNA promoters by ppGpp and the initiating NTP. Cell 118, 311-322 (2004).
8. Kuroda, A., Murphy, H., Cashel, M. & Kornberg, A. Guanosine tetra- and pentaphosphate promote accumulation of inorganic polyphosphate in Escherichia coli. J. Biol. Chem. 272, 21240-21243 (1997).
9. Kuroda, A. et al. Inorganic polyphosphate kinase is required to stimulate protein degradation and for adaptation to amino acid starvation in Escherichia coli. Proc. Natl Acad. Sci. USA 96, 14264-14269 (1999).
10. Kuroda, A. et al. Role of inorganic polyphosphate in promoting ribosomal protein degradation by the Lon protease in E. coli. Science 293, 705-708 (2001).
11. Jishage, M., Kvint, K., Shingler, V. & Nystrom, T. Regulation of σ factor competition by the alarmone ppGpp. Genes Dev. 16, 1260-1270 (2002).
12. N competition for core RNA polymerase. J. Biol. Chem. 278, 1494-1503 (2003).
13. Pandey D. P. & Gerdes, K. Toxin-antitoxin quality control loci are highly abundant in free-living but lost from host-associated prokaryotes. Nucleic Acids Res. 33, 966-976 (2005).
14. Gerdes, K., Moller-Jensen, J., Ebersbach, G., Kruse, T. & Nordstrom, K. Bacterial mitotic machineries. Cell 116, 359-366 (2004).
15. Ogura, T. & Hiraga, S. Mini-F plasmid genes that couple host cell division to plasmid proliferation. Proc. Natl Acad. Sci. USA 80, 4784-4788 (1983).
16. Gerdes, K., Rasmussen, P. B. & Molin, S. Unique type of plasmid maintenance function: postsegregational killing of plasmid-free cells. Proc. Natl Acad. Sci. USA 83, 3116-3120 (1986).
17. Greenfield, T. J. et al. The antisense RNA of the par locus of pAD1 regulates the expression of a 33-amino-acid toxic peptide by an unusual mechanism. Mol. Microbiol. 37, 652-660 (2000).
18. Gerdes, K. et al. Mechanism of postsegregational killing by the hok gene product of the parB system of plasmid R1 and its homology with the relF gene product of the E. coli relB operon. EMBO J. 5, 2023-2029 (1986).
19. Gerdes, K. Toxin-antitoxin modules may regulate synthesis of macromolecules during nutritional stress. J. Bacteriol. 182, 561-572 (2000).
20. Allen, G. C. Jr & Kornberg, A. Fine balance in the regulation of DnaB helicase by DnaC protein in replication in Escherichia coli. J. Biol. Chem. 266, 22096-22101 (1991).
21. Boe, L., Gerdes, K. & Molin, S. Effects of genes exerting growth inhibition and plasmid stability on plasmid maintenance. J. Bacteriol. 169, 4646-4650 (1987).
22. Jensen, R. B., Grohmann, E., Schwab, H., Diaz-Orejas, R. & Gerdes, K. Comparison of ccd of F, parDE of RP4, and parD of R1 using a novel conditional replication control system of plasmid R1. Mol. Microbiol. 17, 211-220 (1995).
23. Miki, T., Yoshioka, K. & Horiuchi, T. Control of cell division by sex factor F in Escherichia coli. I. The 42.84-43.6 F segment couples cell division of the host bacteria with replication of plasmid DNA. J. Mol. Biol. 174, 605-625 (1984).
24. Jaffe, A., Ogura, T. & Hiraga, S. Effects of the ccd function of the F plasmid on bacterial growth. J. Bacteriol. 163, 841-849 (1985).
25. Hiraga, S., Jaffe, A., Ogura, T., Mori, H. & Takahashi, H. F plasmid ccd mechanism in Escherichia coli. J. Bacteriol. 166, 100-104 (1986).
26. Gotfredsen, M. & Gerdes, K. The Escherichia coli relBE genes belong to a new toxin-antitoxin gene family Mol. Microbiol. 29, 1065-1076 (1998).
27. Galvani, C., Terry, J. & Ishiguro, E. E. Purification of the RelB and RelE proteins of Escherichia coli: RelE binds to RelB and to ribosomes. J. Bacteriol. 183, 2700-2703 (2001).
28. Christensen, S. K., Mikkelsen, M., Pedersen, K. & Gerdes, K. RelE, a global inhibitor of translation, is activated during nutritional stress. Proc. Natl Acad. Sci. USA 98, 14328-14333 (2001).
29. Pedersen, K., Christensen, S. K. & Gerdes, K. Rapid induction and reversal of a bacteriostatic condition by controlled expression of toxins and antitoxins. Mol. Microbiol. 45, 501-510 (2002).
30. Smith, A. S. & Rawlings, D. E. The poison-antidote stability system of the broad-host-range Thiobacillus ferrooxidans plasmid pTF-FC2. Mol. Microbiol. 26, 961-970 (1997).
31. Gronlund, H. & Gerdes, K. Toxin-antitoxin systems homologous with relBE of Escherichia coli plasmid P307 are ubiquitous in prokaryotes. J. Mol. Biol. 285, 1401-1415 (1999).
32. Cherny, I. & Gazit, E. The YefM antitoxin defines a family of natively unfolded proteins: implications as a novel antibacterial target. J. Biol. Chem. 279, 8252-8261 (2004).
33. Christensen, S. K. et al. Overproduction of the Lon protease triggers inhibition of translation in Escherichia coli: involvement of the yefM-yoeB toxin-antitoxin system. Mol. Microbiol. 51, 1705-1717 (2004).
34. Grady, R. & Hayes, F. Axe-Txe, a broad-spectrum proteic toxin-antitoxin system specified by a multidrug-resistant, clinical isolate of Enterococcus faecium. Mol. Microbiol. 47, 1419-1432 (2003).
35. Tian, Q. B., Ohnishi, M., Tabuchi, A. & Terawaki, Y. A new plasmid-encoded proteic killer gene system: cloning, sequencing, and analyzing hig locus of plasmid Rts1. Biochem. Biophys. Res. Commun. 220, 280-284 (1996).
36. Tian, Q. B. et al. Specific protein-DNA and protein-protein interaction in the hig gene system, a plasmid-borne proteic killer gene system of plasmid Rts1. Plasmid 45, 63-74 (2001).
37. Gerlitz, M., Hrabak, O. & Schwab, H. Partitioning of broad-host-range plasmid RP4 is a complex system involving site-specific recombination. J. Bacteriol. 172, 6194-6203 (1990).
38. Roberts, R. C. & Helinski, D. R. Definition of a minimal plasmid stabilization system from the broad-host-range plasmid RK2. J. Bacteriol. 174, 8119-8132 (1992).
39. Roberts, R. C., Strom, A. R. & Helinski, D. R. The parDE operon of the broad-host-range plasmid RK2 specifies growth inhibition associated with plasmid loss. J. Mol. Biol. 237, 35-51 (1994).
40. Sobecky, P. A., Easter, C. L., Bear, P. D. & Helinski, D. R. Characterization of the stable maintenance properties of the par region of broad-host-range plasmid RK2. J. Bacteriol. 178, 2086-2093 (1996).
41. Haigermoser, C., Chen, G. Q., Grohmann, E., Hrabak, O. & Schwab, H. Stability of r-microbes: stabilization of plasmid vectors by the partitioning function of broad-host-range plasmid RP4. J. Biotechnol. 28, 291-299 (1993).
42. Sia, E. A., Roberts, R. C., Easter, C., Helinski, D. R. & Figurski, D. H. Different relative importances of the par operons and the effect of conjugal transfer on the maintenance of intact promiscuous plasmid RK2. J. Bacteriol. 177, 2789-2797 (1995).
43. Bravo, A., de Morrontegui, T. G. & Diaz, R. Identification of components of a new stability system of plasmid R1, ParD, that is close to the origin of replication of this plasmid. Mol. Gen. Genet. 210, 101-110 (1987).
44. Tsuchimoto, S., Ohtsubo, H. & Ohtsubo, E. Two genes, pemK and pemI, responsible for stable maintenance of resistance plasmid R100. J. Bacteriol. 170, 1461-1466 (1988).
45. Ruiz-Echevarria, M. J., de la Torre, M. A. & Diaz-Orejas, R. A mutation that decreases the efficiency of plasmid R1 replication leads to the activation of parD, a killer stability system of the plasmid. FEMS Microbiol. Lett. 130, 129-135 (1995).
46. Masuda, Y. & Ohtsubo, E. Mapping and disruption of the chpB locus in Escherichia coli. J. Bacteriol. 176, 5861-5863 (1994).
47. 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. 175, 6850-6856 (1993).
48. Metzger, S. et al. The nucleotide sequence and characterization of the relA gene of Escherichia coli. J. Biol. Chem. 263, 15699-15704 (1988).
49. Lehnherr, H., Maguin, E., Jafri, S. & Yarmolinsky, M. B. Plasmid addiction genes of bacteriophage P1: doc, which causes cell death on curing of prophage, and phd, which prevents host death when prophage is retained. J. Mol. Biol. 233, 414-428 (1993).
50. Lehnherr, H. & Yarmolinsky, M. B. Addiction protein Phd of plasmid prophage P1 is a substrate of the ClpXP serine protease of Escherichia coli. Proc. Natl Acad. Sci. USA 92, 3274-3277 (1995).
51. Gazit, E. & Sauer, R. T. The Doc toxin and Phd antidote proteins of the bacteriophage P1 plasmid addiction system form a heterotrimeric complex. J. Biol. Chem. 274, 16813-16818 (1999).
52. Pomerantsev, A. P. et al. Genetic organization of the Francisella plasmid pRNL 10. Plasmid 46, 210-222 (2001).
53. 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. 183, 2046-2050 (2001).
54. Pullinger, G. D. & Lax, A. J. A Salmonella dublin virulence plasmid locus that affects bacterial growth under nutrient-limited conditions. Mol. Microbiol. 6, 1631-1643 (1992).
55. Sayeed, S., Reaves, L., Radnedge, L. & Austin, S. The stability region of the large virulence plasmid of Shigella flexneri encodes an efficient postsegregational killing system. J. Bacteriol. 182, 2416-2421 (2000).
56. Bloomfield, G. A., Whittle, G., McDonagh, M. B., Katz, M. E. & Cheetham, B. F. Analysis of sequences flanking the vap regions of Dichelobacter nodosus: evidence for multiple integration events, a killer system, and a new genetic element. Microbiology 143, 553-562 (1997).
57. Zhang, Y. X. et al. Characterizaton of a novel toxin-antitoxin module, VapBC, encoded by Leptospira interrogans chromosome. Cell Res. 14, 208-216 (2004).
58. Anantharaman, V. & Aravind, L. New connections in the prokaryotic toxin-antitoxin network: relationship with the eukaryotic nonsense-mediated RNA decay system. Genome Biol. 4, R81 (2003).
59. Clissold, P. M. & Ponting, C. P. PIN domains in nonsense-mediated mRNA decay and RNAi. Curr. Biol. 10, R888-R890 (2000).
60. de la Hoz, A. B. et al. Plasmid copy-number control and better-than-random segregation genes of pSM19035 share a common regulator. Proc. Natl Acad. Sci. USA 97, 728-733 (2000).
61. Ceglowski, P., Boitsov, A., Karamyan, N., Chai, S. & Alonso, J. C. Characterization of the effectors required for stable inheritance of Streptococcus pyogenes pSM19035-derived plasmids in Bacillus subtilis. Mol. Gen. Genet. 241, 579-585 (1993).
62. Camacho, A. G. et al. In vitro and in vivo stability of the E2ζ2 protein complex of the broad host-range Streptococcus pyogenes pSM19035 addiction system. Biol. Chem. 383, 1701-1713 (2002).
63. Meinhart, A., Alonso, J. C., Strater, N. & Saenger, W. Crystal structure of the plasmid maintenance system E/ζ: functional mechanism of toxin ζ and inactivation by E2 ζ2 complex formation. Proc. Natl Acad. Sci. USA 100, 1661-1666 (2003).
64. Chang, S. & Cohen, S. N. In vivo site-specific genetic recombination promoted by the EcoRl restriction endonuclease. Proc. Natl Acad. Sci. USA 74, 4811-4815 (1977).
65. Bickle, T. A. & Kruger, D. H. Biology of DNA restriction. Microbiol. Rev. 57, 434-450 (1993).
66. Naito, T., Kusano, K. & Kobayashi, I. Selfish behavior of restriction-modification systems. Science 267, 897-899 (1995).
67. Black, D. S., Kelly, A. J., Mardis, M. J. & Moyed, H. S. Structure and organization of hip, an operon that affects lethality due to inhibition of peptidoglycan or DNA synthesis. J. Bacteriol. 173, 5732-5739 (1991).
68. Black, D. S., Irwin, B. & Moyed, H. S. Autoregulation of hip, an operon that affects lethality due to inhibition of peptidoglycan or DNA synthesis. J. Bacteriol. 176, 4081-4091 (1994).
69. Falla, T. J. & Chopra, I. Stabilization of Rhizobium symbiosis plasmids. Microbiology 145, 515-516 (1999).
70. Korch, S. B., Henderson, T. A. & Hill, T. M. Characterization of the hipA7 allele of Escherichia coli and evidence that high persistence is governed by (p)ppGpp synthesis. Mol. Microbiol. 50, 1199-1213 (2003).
71. Balaban, N. Q., Merrin, J., Chait, R., Kowalik, L. & Leibler, S. Bacterial persistence as a phenotypic switch. Science 305, 1622-1625 (2004).
72. Mittenhuber, G. Occurrence of mazEF-like antitoxin/toxin systems in bacteria. J. Mol. Microbiol. Biotechnol. 1, 295-302 (1999).
73. Cole, S. T. et al. Massive gene decay in the leprosy bacillus. Nature 409, 1007-1011 (2001).
74. Bernard, P. & Couturier, M. Cell killing by the F plasmid CcdB protein involves poisoning of DNA-topoisomerase II complexes. J. Mol. Biol. 226, 735-745 (1992).
75. Maki, S., Takiguchi, S., Miki, T. & Horiuchi, T. Modulation of DNA supercoiling activity of Escherichia coli DNA gyrase by F plasmid proteins. Antagonistic actions of LetA (CcdA) and LetD (CcdB) proteins. J. Biol. Chem. 267, 12244-12251 (1992).
76. Critchlow, S. E. et al. The interaction of the F plasmid killer protein, CcdB, with DNA gyrase: induction of DNA cleavage and blocking of transcription. J. Mol. Biol. 273, 826-839 (1997).
77. Bernard, P. et al. The F plasmid CcdB protein induces efficient ATP-dependent DNA cleavage by gyrase. J. Mol. Biol. 234, 534-541 (1993).
78. Bahassi, E. M., Salmon, M. A., Van, M. L., Bernard, P. & Couturier, M. F plasmid CcdB killer protein: ccdB gene mutants coding for non-cytotoxic proteins which retain their regulatory functions. Mol. Microbiol. 15, 1031-1037 (1995).
79. Hargreaves, D. et al. Structural and functional analysis of the kid toxin protein from E. coli plasmid R1. Structure. (Camb.) 10, 1425-1433 (2002).
80. Kamada, K., Hanaoka, F. & Burley, S. K. Crystal structure of the MazE/MazF complex: molecular bases of antidote-toxin recognition. Mol. Cell 11, 875-884 (2003).
81. Jiang, Y., Pogliano, J., Helinski, D. R. & Konieczny, I. ParE toxin encoded by the broad-host-range plasmid RK2 is an inhibitor of Escherichia coli gyrase. Mol. Microbiol. 44, 971-979 (2002).
82. Pedersen, K. et al. The bacterial toxin RelE displays codon-specific cleavage of mRNAs in the ribosomal A site. Cell 112, 131-140 (2003).
83. Christensen, S. K. & Gerdes, K. RelE toxins from bacteria and Archaea cleave mRNAs on translating ribosomes, which are rescued by tmRNA. Mol. Microbiol. 48, 1389-1400 (2003).
84. Zavialov, A. V., Mora, L., Buckingham, R. H. & Ehrenberg, M. Release of peptide promoted by the GGQ motif of class 1 release factors regulates the GTPase activity of RF3. Mol. Cell 10, 789-798 (2002).
85. Christensen, S. K., Pedersen, K., Hansen, F. G. & Gerdes, K. Toxin-antitoxin loci as stress-response-elements: ChpAK/MazF and ChpBK cleave translated RNAs and are counteracted by tmRNA. J. Mol. Biol. 332, 809-819 (2003).
86. Zhang, Y. et al. MazF cleaves cellular mRNAs specifically at ACA to block protein synthesis in Escherichia coli. Mol. Cell 12, 913-923 (2003).
87. Zhang, Y., Zhang, J., Hara, H., Kato, I. & Inouye, M. Insights into the mRNA cleavage mechanism by MazF, an mRNA interferase. J. Biol. Chem. 280, 3143-3150 (2005).
88. Ruiz-Echevarria, M. J., Gimenez-Gallego, G., Sabariegos-Jareno, R. & Diaz-Orejas, R. Kid, a small protein of the parD stability system of plasmid R1, is an inhibitor of DNA replication acting at the initiation of DNA synthesis. J. Mol. Biol. 247, 568-577 (1995).
89. Zhang, J., Zhang, Y., Zhu, L., Suzuki, M. & Inouye, M. Interference of mRNA function by sequence-specific endoribonuclease PemK. J. Biol. Chem. 279, 20678-20684 (2004).
90. Keiler, K. C., Waller, P. R. & Sauer, R. T. Role of a peptide tagging system in degradation of proteins synthesized from damaged messenger RNA. Science 271, 990-993 (1996).
91. Ivanova, N., Pavlov, M. Y., Felden, B. & Ehrenberg, M. Ribosome rescue by tmRNA requires truncated mRNAs. J. Mol Biol. 338, 33-41 (2004).
92. Loris, R. et al. Crystal structure of CcdB, a topoisomerase poison from E. coli. J. Mol. Biol. 285, 1667-1677 (1999).
93. Afif, H., Allali, N., Couturier, M. & Van Melderen, L. The ratio between CcdA and CcdB modulates the transcriptional repression of the ccd poison-antidote system. Mol. Microbiol. 41, 73-82 (2001).
94. Santos-Sierra, S., Pardo-Abarrio, C., Giraldo, R. & Diaz-Orejas, R. Genetic identification of two functional regions in the antitoxin of the parD killer system of plasmid R1. FEMS Microbiol. Lett. 206, 115-119 (2002).
95. Zhang, J., Zhang, Y. & Inouye, M. Characterization of the interactions within the mazEF addiction module of Escherichia coli. J. Biol. Chem. 278, 32300-32306 (2003).
96. Smith, J. A. & Magnuson, R. D. Modular organization of the Phd repressor/antitoxin protein. J. Bacteriol. 186, 2692-2698 (2004).
97. Lemonnier, M., Santos-Sierra, S., Pardo-Abarrio, C. & Diaz-Orejas, R. Identification of residues of the kid toxin involved in autoregulation of the parD system. J. Bacteriol. 186, 240-243 (2004).
98. Raumann, B. E., Rould, M. A., Pabo, C. O. & Sauer, R. T. DNA recognition by β-sheets in the Arc repressor-operator crystal structure. Nature 367, 754-757 (1994).
99. Oberer, M., Zangger, K., Prytulla, S. & Keller, W. The anti-toxin ParD of plasmid RK2 consists of two structurally distinct moieties and belongs to the ribbon-helix-helix family of DNA-binding proteins. Biochem. J. 361, 41-47 (2002).
100. Vaughn, J. L., Feher, V., Naylor, S., Strauch, M. A. & Cavanagh, J. Novel DNA binding domain and genetic regulation model of Bacillus subtilis transition state regulator abrB. Nature Struct. Biol. 7, 1139-1146 (2000).
101. Salmon, M. A., Van Melderen, L., Bernard, P. & Couturier, M. The antidote and autoregulatory functions of the F plasmid CcdA protein: a genetic and biochemical survey. Mol. Gen. Genet. 244, 530-538 (1994).
102. Davis, T. L., Helinski, D. R. & Roberts, R. C. Transcription and autoregulation of the stabilizing functions of broad-host-range plasmid RK2 in Escherichia coli, Agrobacterium tumefaciens and Pseudomonas aeruginosa. Mol. Microbiol. 6, 1981-1994 (1992).
103. Eberl, L., Givskov, M. & Schwab, H. The divergent promoters mediating transcription of the par locus of plasmid RP4 are subject to autoregulation. Mol. Microbiol. 6, 1969-1979 (1992).
104. Magnuson, R., Lehnherr, H., Mukhopadhyay, G. & Yarmolinsky, M. B. Autoregulation of the plasmid addiction operon of bacteriophage P1. J. Biol. Chem. 271, 18705-18710 (1996).
105. 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. 276, 5975-5984 (2001).
106. Magnuson, R. & Yarmolinsky, M. B. Corepression of the P1 addiction operon by Phd and Doc. J. Bacteriol. 180, 6342-6351 (1998).
107. Tam, J. E. & Kline, B. C. Control of the ccd operon in plasmid F. J. Bacteriol. 171, 2353-2360 (1989).
108. Tam, J. E. & Kline, B. C. The F plasmid ccd autorepressor is a complex of CcdA and CcdB proteins. Mol. Gen. Genet. 219, 26-32 (1989).
109. Roberts, R. C., Spangler, C. & Helinski, D. R. Characteristics and significance of DNA binding activity of plasmid stabilization protein ParD from the broad host-range plasmid RK2. J. Biol. Chem. 268, 27109-27117 (1993).
110. van Melderen, L., Bernard, P. & Couturier, M. Lon-dependent proteolysis of CcdA is the key control for activation of CcdB in plasmid-free segregant bacteria. Mol. Microbiol. 11, 1151-1157 (1994).
111. Johnson, E. P., Strom, A. R. & Helinski, D. R. Plasmid RK2 toxin protein ParE: purification and interaction with the ParD antitoxin protein. J. Bacteriol. 178, 1420-1429 (1996).
112. Gottesman, S. Proteases and their targets in Escherichia coli. Annu. Rev. Genet. 30, 465-506 (1996).
113. Christensen, S. K. & Gerdes, K. Delayed-relaxed response explained by hyperactivation of RelE. Mol. Microbiol. 53, 587-597 (2004).
114. 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. USA 93, 6059-6063 (1996).
115. van Melderen, L. et al. ATP-dependent degradation of CcdA by Lon protease. Effects of secondary structure and heterologous subunit interactions. J. Biol. Chem. 271, 27730-27738 (1996).
116. Diderichsen, B., Fiil, N. P. & Lavelle, R. Genetics of the relB locus in Escherichia coli. J. Bacteriol. 131, 30-33 (1977).
117. O'Farrell, P. H. The suppression of defective translation by ppGpp and its role in the stringent response. Cell 14, 545-557 (1978).
118. Nystrom, T. Role of guanosine tetraphosphate in gene expression and the survival of glucose or seryl-transfer RNA starved cells of Escherichia coli K12. Mol. Gen. Genet. 245, 355-362 (1994).
119. Nystrom, T. Conditional senescence in bacteria: death of the immortals. Mol. Microbiol. 48, 17-23 (2003).
120. Nystrom, T. Starvation, cessation of growth and bacterial aging. Curr. Opin. Microbiol. 2, 214-219 (1999).
121. Nystrom, T. Stationary-phase physiology. Annu. Rev. Microbiol. 58, 161-181 (2004).
122. Hazan, R., Sat, B. & Engelberg-Kulka, H. Escherichia coli mazEF-mediated cell death is triggered by various stressful conditions. J. Bacteriol. 186, 3663-3669 (2004).
123. Sat, B., Reches, M. & Engelberg-Kulka, H. The Escherichia coli mazEF suicide module mediates thymineless death. J. Bacteriol. 185, 1803-1807 (2003).
124. Sat, B. et al. Programmed cell death in Escherichia coli: some antibiotics can trigger mazEF lethality. J. Bacteriol. 183, 2041-2045 (2001).
125. 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 272, 227-234 (2004).
126. Jensen, R. B. & Gerdes, K. Programmed cell death in bacteria: proteic plasmid stabilization systems. Mol. Microbiol. 17, 205-210 (1995).
127. Rowe-Magnus, D. A., Guerout, A. M., Biskri, L., Bouige, P. & Mazel, D. Comparative analysis of superintegrons: engineering extensive genetic diversity in the Vibrionaceae. Genome Res. 13, 428-442 (2003).
128. Engelberg-Kulka, H., Sat, B., Reches, M., Amitai, S. & Hazan, R. Bacterial programmed cell death systems as targets for antibiotics. Trends Microbiol. 12, 66-71 (2004).
129. Gerdes, K. The parB (hok/sok) locus of plasmid R1: a general purpose plasmid stabilization system. Bio/Technology 6, 1402-1405 (1988).
130. Pecota, D. C., Kim, C. S., Wu, K., Gerdes, K. & Wood, T. K. Combining the hok/sok, parDE, and pnd postsegregational killer loci to enhance plasmid stability. Appl. Environ. Microbiol. 63, 1917-1924 (1997).
131. Bernard, P., Gabant, P., Bahassi, E. M. & Couturier, M. Positive-selection vectors using the F plasmid ccdB killer gene. Gene 148, 71-74 (1994).
132. Ramos, J. L. et al. The behavior of bacteria designed for biodegradation. Biotechnology 12, 1349-1356 (1994).
133. Vogel, U. & Jensen, K. F. Effects of guanosine 3′,5′-bisdiphosphate (ppGpp) on rate of transcription elongation in isoleucine-starved Escherichia coli. J. Biol. Chem. 269, 16236-16241 (1994).
134. Robinson, N. P. et al. Identification of two origins of replication in the single chromosome of the archaeon Sulfolobus solfataricus. Cell 116, 25-38 (2004).