Structural overview of toxin-antitoxin systems in infectious bacteria: A target for developing antimicrobial agents

Biochimica et Biophysica Acta - Proteins and Proteomics

Volumn 1834, Issue 6, 2013, Pages 1155-1167

  Park, Sung Jean ^a   Son, Woo Sung ^b   Lee, Bong Jin ^c  

^a Gachon University College of Medicine   (South Korea)

^b CHA University   (South Korea)

^c Seoul National University   (South Korea)

Author keywords

NMR X ray; Structure; TA system

Indexed keywords

ANTIBIOTIC AGENT; ANTITOXIN; BACTERIAL PROTEIN; BACTERIAL TOXIN; DNA TOPOISOMERASE (ATP HYDROLYSING); MESSENGER RNA; PHOSPHOTRANSFERASE; RIBONUCLEASE; RNA; TOXIN; TOXIN ANTITOXIN; TOXIN ANTITOXIN TYPE I; TOXIN ANTITOXIN TYPE II; TOXIN ANTITOXIN TYPE III; UNCLASSIFIED DRUG;

ALPHA HELIX; BACILLUS SUBTILIS; BACTERIAL CELL; BACTERIAL GENE; BACTERIAL STRAIN; BACTERIUM; BIOINFORMATICS; CELL DEATH; CELL SURVIVAL; COMPLEX FORMATION; CRYSTAL STRUCTURE; ERWINIA; ESCHERICHIA COLI; EUKARYOTE; GENE EXPRESSION; GENE LOCUS; GENE REPLICATION; GENE TARGETING; HYDROPHOBICITY; MOLECULE; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN PHOSPHORYLATION; PROTEIN STABILITY; PROTEOMICS; REVIEW; RIBOSOME; RNA CLEAVAGE; RNA TRANSLATION; TOXIN STRUCTURE; X RAY CRYSTALLOGRAPHY;

AMINO ACID SEQUENCE; ANTI-INFECTIVE AGENTS; ANTITOXINS; BACTERIA; BACTERIAL PROTEINS; BACTERIAL TOXINS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA;

BACTERIA (MICROORGANISMS);

EID: 84877081375     PISSN: 15709639     EISSN: 18781454     Source Type: Journal    
DOI: 10.1016/j.bbapap.2013.02.027     Document Type: Review

References (117)

1. Y. Yamaguchi, J.H. Park, and M. Inouye Toxin-antitoxin systems in bacteria and archaea Annu. Rev. Genet. 45 2011 61 79
2. L. Van Melderen, and M. Saavedra De Bast Bacterial toxin-antitoxin systems: More than selfish entities? PLoS Genet. 5 2009 e1000437
3. V. Kunin, and C.A. Ouzounis The balance of driving forces during genome evolution in prokaryotes Genome Res. 13 2003 1589 1594
4. D.P. Pandey, and K. Gerdes Toxin-antitoxin loci are highly abundant in free-living but lost from host-associated prokaryotes Nucleic Acids Res. 33 2005 966 976
5. E.M. Bahassi, M.H. O'Dea, N. Allali, J. Messens, M. Gellert, and M. Couturier Interactions of CcdB with DNA gyrase. Inactivation of Gyra, poisoning of the gyrase-DNA complex, and the antidote action of CcdA J. Biol. Chem. 274 1999 10936 10944
6. Y. Yamaguchi, and M. Inouye mRNA interferases, sequence-specific endoribonucleases from the toxin-antitoxin systems Prog. Mol. Biol. Transl. Sci. 85 2009 467 500
7. A.J. Muñoz-Gómez, S. Santos-Sierra, A. Berzal-Herranz, M. Lemonnier, and R. Díaz-Orejas Insights into the specificity of RNA cleavage by the Escherichia coli MazF toxin FEBS Lett. 567 2004 316 320
8. V.L. Arcus, J.L. McKenzie, J. Robson, and G.M. Cook The PIN-domain ribonucleases and the prokaryotic VapBC toxin-antitoxin array Protein Eng. Des. Sel. 24 2011 33 40
9. H. Mutschler, and A. Meinhart ε/ζ systems: Their role in resistance, virulence, and their potential for antibiotic development J. Mol. Med. (Berl) 89 2011 1183 1194
10. M.A. Schumacher, K.M. Piro, W. Xu, S. Hansen, K. Lewis, and R.G. Brennan Molecular mechanisms of HipA-mediated multidrug tolerance and its neutralization by HipB Science 323 2009 396 401
11. F.F. Correia, A. D'Onofrio, T. Rejtar, L. Li, B.L. Karger, K. Makarova, E.V. Koonin, and K. Lewis Kinase activity of overexpressed HipA is required for growth arrest and multidrug tolerance in Escherichia coli J. Bacteriol. 188 2006 8360 8367
12. C. Unoson, and E.G. Wagner A small SOS-induced toxin is targeted against the inner membrane in Escherichia coli Mol. Microbiol. 70 2008 258 270
13. H. Engelberg-Kulka, S. Amitai, I. Kolodkin-Gal, and R. Hazan Bacterial programmed cell death and multicellular behavior in bacteria PLoS Genet. 2 2006 e135
14. K. Gerdes, S.K. Christensen, and A. Løbner-Olesen Prokaryotic toxin-antitoxin stress response loci Nat. Rev. Microbiol. 3 2005 371 382
15. K. Gerdes, and E.G. Wagner RNA antitoxins Curr. Opin. Microbiol. 10 2007 117 124
16. T. Franch, A.P. Gultyaev, and K. Gerdes Programmed cell death by hok/sok of plasmid R1: Processing at the hok mRNA 30-end triggers structural rearrangements that allow translation and antisense RNA binding J. Mol. Biol. 273 1997 38 51
17. E. Aizenman, H. Engelberg-Kulka, and G. Glaser 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. 93 1996 6059 6063
18. M. Kawano, L. Aravind, and G. Storz An antisense RNA controls synthesis of an SOS-induced toxin evolved from an antitoxin Mol. Microbiol. 64 2007 738 754
19. M. Kawano, T. Oshima, H. Kasai, and H. Mori Molecular characterization of long direct repeat (LDR) sequences expressing a stable mRNA encoding for a 35-amino-acid cell-killing peptide and a cis-encoded small antisense RNA in Escherichia coli Mol. Microbiol. 45 2002 333 349
20. K. Pedersen, A.V. Zavialov, M.Y. Pavlov, J. Elf, K. Gerdes, and M. Ehrenberg The bacterial toxin RelE displays codon-specific cleavage of mRNAs in the ribosomal A site Cell 112 2003 131 140
21. T.R. Blower, F.L. Short, F. Rao, K. Mizuguchi, X.Y. Pei, P.C. Fineran, B.F. Luisi, and G.P. Salmond Identification and classification of bacterial Type III toxin-antitoxin systems encoded in chromosomal and plasmid genomes Nucleic Acids Res. 40 2012 6158 6173
22. P.C. Fineran, T.R. Blower, I.J. Foulds, D.P. Humphreys, K.S. Lilley, and G.P. Salmond The phage abortive infection system, ToxIN, functions as a protein-RNA toxin-antitoxin pair Proc. Natl. Acad. Sci. U. S. A. 106 2009 894 899
23. E.M. Fozo, M.R. Hemm, and G. Storz Small toxic proteins and the antisense RNAs that repress them Microbiol. Mol. Biol. Rev. 72 2008 579 589
24. F. Hayes Toxins-antitoxins: Plasmid maintenance, programmed cell death, and cell cycle arrest Science 301 2003 1496 1499
25. K. Gerdes, J.E. Larsen, and S. Molin Stable inheritance of plasmid R1 requires two different loci J. Bacteriol. 161 1985 292 298
26. S.M. Loh, D.S. Cram, and R.A. Skurray Nucleotide sequence and transcriptional analysis of a third function (Flm) involved in F-plasmid maintenance Gene 66 1988 259 268
27. Y. Onishi F factor promotes turnover of stable RNA in Escherichia coli Science 187 1975 257 258
28. Y. Ohnishi, H. Iguma, T. Ono, H. Nagaishi, and A.J. Clark Genetic mapping of the F plasmid gene that promotes degradation of stable ribonucleic acid in Escherichia coli J. Bacteriol. 132 1977 784 789
29. S. Akimoto, and Y. Ohnishi R483 and F plasmid genes promoting RNA degradation: Comparative restriction mapping Microbiol. Immunol. 26 1982 779 793
30. Y. Ohnishi, and S. Akimoto I-like R plasmids promote degradation of stable ribonucleic acid in Escherichia coli J. Bacteriol. 144 1980 833 835
31. R. Ito, and Y. Ohnishi The roles of RNA polymerase and RNAase I in stable RNA degradation in Escherichia coli carrying the srnB + gene Biochim. Biophys. Acta 739 1983 27 34
32. K.E. Weaver, K.D. Jensen, A. Colwell, and S.I. Sriram Functional analysis of the Enterococcus faecalis plasmid pAD1-encoded stability determinant par Mol. Microbiol. 20 1996 53 63
33. K.E. Rudd Novel intergenic repeats of Escherichia coli K-12 Res. Microbiol. 150 1999 653 664
34. E.M. Fozo, M. Kawano, F. Fontaine, Y. Kaya, K.S. Mendieta, K.L. Jones, A. Ocampo, K.E. Rudd, and G. Storz Repression of small toxic protein synthesis by the Sib and OhsC small RNAs Mol. Microbiol. 70 2008 1076 1093
35. J.M. Silvaggi, J.B. Perkins, and R. Losick Small untranslated RNA antitoxin in Bacillus subtilis J. Bacteriol. 187 2005 6641 6650
36. M. Kawano, A.A. Reynolds, J. Miranda-Rios, and G. Storz Detection of 5′- and 3′-UTR-derived small RNAs and cis-encoded antisense RNAs in Escherichia coli Nucleic Acids Res. 33 2005 1040 1050
37. L. Argaman, R. Hershberg, J. Vogel, G. Bejerano, E.G. Wagner, H. Margalit, and S. Altuvia Novel small RNA-encoding genes in the intergenic regions of Escherichia coli Curr. Biol. 11 2001 941 950
38. J. Vogel, L. Argaman, E.G. Wagner, and S. Altuvia The small RNA IstR inhibits synthesis of an SOS-induced toxic peptide Curr. Biol. 14 2004 2271 2276
39. R.A. Wozniak, and M.K. Waldor A toxin-antitoxin system promotes the maintenance of an integrative conjugative element PLoS Genet. 5 2009 e1000439
40. F. Hayes, and L. Van Melderen Toxins-antitoxins: Diversity, evolution and function Crit. Rev. Biochem. Mol. 46 2011 386 408
41. L. Buts, J. Lah, M.H. Dao-Thi, L. Wyns, and R. Loris Toxin-antitoxin modules as bacterial metabolic stress managers Trends Biochem. Sci. 30 2005 672 679
42. Y. Shao, E.M. Harrison, D. Bi, C. Tai, X. He, H.Y. Ou, K. Rajakumar, and Z. Deng TADB: A web-based resource for Type 2 toxin-antitoxin loci in bacteria and archaea Nucleic Acids Res. 39 2011 D606 D611
43. E.W. Sevin, and F. Barloy-Hubler RASTA-bacteria: A web-based tool for identifying toxin-antitoxin loci in prokaryotes Genome Biol. 8 2007 R155
44. M. Christensen-Dalsgaard, M.G. Jorgensen, and K. Gerdes Three new RelE-homologous mRNA interferases of Escherichia coli differentially induced by environmental stresses Mol. Microbiol. 75 2010 333 348
45. K. Kamada, and F. Hanaoka Conformational change in the catalytic site of the ribonuclease YoeB toxin by YefM antitoxin Mol. Cell. 19 2005 497 509
46. B.L. Brown, S. Grigoriu, Y. Kim, J.M. Arruda, A. Davenport, T.K. Wood, W. Peti, and R. Page Three dimensional structure of the MqsR:MqsA complex: A novel TA pair comprised of a toxin homologous to RelE and an antitoxin with unique properties PloS Pathog. 5 2009 e1000706
47. O. Schmidt, V.J. Schuenemann, N.J. Hand, T.J. Silhavy, J. Martin, A.N. Lupas, and S. Djuranovic prlF and yhaV encode a new toxin-antitoxin system in Escherichia coli J. Mol. Biol. 372 2007 894 905
48. P.S. Miclea, M. Peter, G. Vegh, G. Cinege, E. Kiss, G. Varo, I. Horvath, and I. Dusha Atypical transcriptional regulation and role of a new toxin-antitoxin-like module and its effect on the lipid composition of Bradyrhizobium japonicum Mol. Plant Microbe Interact. 23 2010 638 650
49. R. Hallez, D. Geeraerts, Y. Sterckx, N. Mine, R. Loris, and L. Van Melderen New toxins homologous to ParE belonging to three-component toxin-antitoxin systems in Escherichia coli O157:H7 Mol. Microbiol. 76 2010 719 732
50. A.B. de la Hoz, S. Ayora, I. Sitkiewicz, S. Fernandez, R. Pankiewicz, J.C. Alonso, and P. Ceglowski Plasmid copy-number control and better-than-random segregation genes of pSM19035 share a common regulator Proc. Natl. Acad. Sci. U. S. A. 97 2000 728 733
51. P. Bernard, K.E. Kezdy, L. Van Melderen, J. Steyaert, L. Wyns, M.L. Pato, P.N. Higgins, and M. Couturier The F plasmid CcdB protein induces efficient ATP-dependent DNA cleavage by gyrase J. Mol. Biol. 234 1993 534 541
52. S.K. Christensen, and K. Gerdes RelE toxins from bacteria and Archaea cleave mRNAs on translating ribosomes, which are rescued by tmRNA Mol. Microbiol. 48 2003 1389 1400
53. Y. Zhang, J. Zhang, H. Hara, I. Kato, and M. Inouye Insights into the mRNA cleavage mechanism by MazF, an mRNA interferase J. Biol. Chem. 280 2005 3143 3150
54. Y. Zhang, J. Zhang, K.P. Hoeflich, M. Ikura, G. Qing, and M. Inouye MazF cleaves cellular mRNAs specifically at ACA to block protein synthesis in Escherichia coli Mol. Cell 12 2003 913 923
55. P.A. Sobecky, C.L. Easter, P.D. Bear, and D.R. Helinski Characterization of the stable maintenance properties of the par region of broad-host-range plasmid RK2 J. Bacteriol. 178 1996 2086 2093
56. R. Hazan, B. Sat, M. Reches, and H. Engelberg-Kulka Postsegregational killing mediated by the P1 phage "addiction module" phd-doc requires the Escherichia coli programmed cell death system mazEF J. Bacteriol. 183 2001 2046 2050
57. M. Liu, Y. Zhang, M. Inouye, and N.A. Woychik Bacterial addiction module toxin Doc inhibits translation elongation through its association with the 30S ribosomal subunit Proc. Natl. Acad. Sci. U. S. A. 105 2008 5885 5890
58. V. Anantharaman, and L. Aravind New connections in the prokaryotic toxin-antitoxin network: Relationship with the eukaryotic nonsense-mediated RNA decay system Genome Biol. 4 2003 R81
59. D.A. Daines, M.H. Wu, and S.Y. Yuan VapC-1 of nontypeable Haemophilus influenzae is a ribonuclease J. Bacteriol. 189 2007 5041 5048
60. Q.B. Tian, M. Ohnishi, T. Murata, K. Nakayama, Y. Terawaki, and T. Hayashi Specific protein-DNA and protein-protein interaction in the hig gene system, a plasmid-borne proteic killer gene system of plasmid Rts1 Plasmid 45 2001 63 74
61. M. Christensen-Dalsgaard, and K. Gerdes Two higBA loci in the Vibrio cholerae superintegron encode mRNA cleaving enzymes and can stabilize plasmids Mol. Microbiol. 62 2006 397 411
62. P.P. Budde, B.M. Davis, J. Yuan, and M.K. Waldor Characterization of a higBA toxin-antitoxin locus in Vibrio cholerae J. Bacteriol. 189 2007 491 500
63. S.B. Korch, and T.M. Hill Ectopic overexpression of wild-type and mutant hipA genes in Escherichia coli: Effects on macromolecular synthesis and persister formation J. Bacteriol. 188 2006 3826 3836
64. T.R. Blower, X.Y. Pei, F.L. Short, P.C. Fineran, D.P. Humphreys, B.F. Luisi, and G.P. Salmond A processed noncoding RNA regulates an altruistic bacterial antiviral system Nat. Struct. Mol. Biol. 18 2011 185 190
65. T.R. Blower, P.C. Fineran, M.J. Johnson, I.K. Toth, D.P. Humphreys, and G.P. Salmond Mutagenesis and functional characterization of the RNA and protein components of the toxIN abortive infection and toxin-antitoxin locus of Erwinia J. Bacteriol. 191 2009 6029 6039
66. D.C. Pecota, and T.K. Wood Exclusion of T4 phage by the hok/sok killer locus from plasmid R1 J. Bacteriol. 178 1996 2044 2050
67. H. Engelberg-Kulka, B. Sat, M. Reches, S. Amitai, and R. Hazan Bacterial programmed cell death systems as targets for antibiotics Trends Microbiol. 12 2004 66 71
68. L. Zhu, J.D. Sharp, H. Kobayashi, N.A. Woychik, and M. Inouye Noncognate Mycobacterium tuberculosis toxin-antitoxins can physically and functionally interact J. Biol. Chem. 285 2010 39732 39738
69. H.R. Ramage, L.E. Connolly, and J.S. Cox Comprehensive functional analysis of Mycobacterium tuberculosis toxin-antitoxin systems: Implications for pathogenesis, stress responses, and evolution PLoS Genet. 5 2009 e1000767
70. V.L. Arcus, P.B. Rainey, and S.J. Turner The PIN-domain toxin-antitoxin array in mycobacteria Trends Microbiol. 13 2005 360 365
71. L. Miallau, M. Faller, J. Chiang, M. Arbing, F. Guo, D. Cascio, and D. Eisenberg Structure and proposed activity of a member of the VapBC family of toxin-antitoxin systems. VapBC-5 from Mycobacterium tuberculosis J. Biol. Chem. 284 2009 276 283
72. S.B. Korch, H. Contreras, and J.E. Clark-Curtiss Three Mycobacterium tuberculosis Rel toxin-antitoxin modules inhibit mycobacterial growth and are expressed in infected human macrophages J. Bacteriol. 191 2009 1618 1630
73. P. Carroll, A.C. Brown, A.R. Hartridge, and T. Parish Expression of Mycobacterium tuberculosis Rv1991c using an arabinose-inducible promoter demonstrates its role as a toxin FEMS Microbiol. Lett. 274 2007 73 82
74. A. Gupta Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis FEMS Microbiol. Lett. 290 2009 45 53
75. P. Kumar, B. Issac, E.J. Dodson, J.P. Turkenburg, and S.C. Mande Crystal structure of Mycobacterium tuberculosis YefM antitoxin reveals that it is not an intrinsically unstructured protein J. Mol. Biol. 383 2008 482 493
76. L. Zhao, and J. Zhang Biochemical characterization of a chromosomal toxin-antitoxin system in Mycobacterium tuberculosis FEBS Lett. 582 2008 710 714
77. L. Zhu, Y. Zhang, J.S. Teh, J. Zhang, N. Connell, H. Rubin, and M. Inouye Characterization of mRNA interferases from Mycobacterium tuberculosis J. Biol. Chem. 281 2006 18638 18643
78. R. Singh, C.E. Barry 3rd, and H.I. Boshoff The three RelE homologs of Mycobacterium tuberculosis have individual, drug-specific effects on bacterial antibiotic tolerance J. Bacteriol. 192 2010 1279 1291
79. K.S. Winther, and K. Gerdes Enteric virulence associated protein VapC inhibits translation by cleavage of initiator tRNA Proc. Natl. Acad. Sci. U. S. A. 108 2011 7403 7407
80. V.L. Arcus, K. Backbro, A. Roos, E.L. Daniel, and E.N. Baker Distant structural homology leads to the functional characterization of an archaeal PIN domain as an exonuclease J. Biol. Chem. 279 2004 16471 16478
81. R.D. Bunker, J.L. McKenzie, E.N. Baker, and V.L. Arcus Crystal structure of PAE0151 from Pyrobaculum aerophilum, a PIN-domain (VapC) protein from a toxin-antitoxin operon Proteins 72 2008 510 518
82. K. Mattison, J.S. Wilbur, M. So, and R.G. Brennan Structure of FitAB from Neisseria gonorrhoeae bound to DNA reveals a tetramer of toxin-antitoxin heterodimers containing pin domains and ribbon-helix-helix motifs J. Biol. Chem. 281 2006 37942 37951
83. B.A. Ahidjo, D. Kuhnert, J.L. McKenzie, E.E. Machowski, B.G. Gordhan, V. Arcus, G.L. Abrahams, and V. Mizrahi VapC toxins from Mycobacterium tuberculosis are ribonucleases that differentially inhibit growth and are neutralized by cognate VapB antitoxins PLoS One 6 2011 e21738
84. M.D. Taylor, and L.M. Napolitano Methicillin-resistant Staphylococcus aureus infections in vascular surgery: Increasing prevalence Surg. Infect. 5 2004 180 187
85. N.P. Donegan, and A.L. Cheung Regulation of the mazEF toxin-antitoxin module in Staphylococcus aureus and its impact on sigB expression J. Bacteriol. 191 2009 2795 2805
86. D.A. Rowe-Magnus, A.M. Guerout, L. Biskri, P. Bouige, and D. Mazel Comparative analysis of superintegrons: Engineering extensive genetic diversity in the Vibrionaceae Genome Res. 13 2003 428 442
87. B. Sat, R. Hazan, T. Fisher, H. Khaner, G. Glaser, and H. Engelberg-Kulka Programmed cell death in Escherichia coli: Some antibiotics can trigger mazEF lethality J. Bacteriol. 183 2001 2041 2045
88. B. Sat, M. Reches, and H. Engelberg-Kulka The Escherichia coli mazEF suicide module mediates thymineless death J. Bacteriol. 185 2003 1803 1807
89. T.R. Blower, G.P. Salmond, and B.F. Luisi Balancing at survival's edge: The structure and adaptive benefits of prokaryotic toxin-antitoxin partners Curr. Opin. Struct. Biol. 21 2011 109 118
90. F.C. Bernstein, T.F. Koetzle, G.J. Williams, E.F. Meyer Jr., M.D. Brice, J.R. Rodgers, O. Kennard, T. Shimanouchi, and M. Tasumi The Protein Data Bank: A computer-based archival file for macromolecular structures J. Mol. Biol. 112 1977 535 542
91. E.F. Pettersen, T.D. Goddard, C.C. Huang, G.S. Couch, D.M. Greenblatt, E.C. Meng, and T.E. Ferrin UCSF Chimera-a visualization system for exploratory research and analysis J. Comp. Chem. 25 2004 1605 1612
92. C. Dienemann, A. Boggild, K.S. Winther, K. Gerdes, and D.E. Brodersen Crystal structure of the VapBC toxin-antitoxin complex from Shigella flexneri reveals a hetero-octameric DNA-binding assembly J. Mol. Biol. 414 2011 713 722
93. J.S. Wilbur, P.T. Chivers, K. Mattison, L. Potter, R.G. Brennan, and M. So Neisseria gonorrhoeae FitA interacts with FitB to bind DNA through its ribbon-helix-helix motif Biochemistry 44 2005 12515 12524
94. J. Robson, J.L. McKenzie, R. Cursons, G.M. Cook, and V.L. Arcus The vapBC operon from Mycobacterium smegmatis is an autoregulated toxin-antitoxin module that controls growth via inhibition of translation J. Mol. Biol. 390 2009 353 367
95. M. Bodogai, S. Ferenczi, D. Bashtovyy, P. Miclea, P. Papp, and I. Dusha The ntrPR operon of Sinorhizobium meliloti is organized and functions as a toxin-antitoxin module Mol. Plant Microbe Interact. 19 2006 811 822
96. K. Kamada, F. Hanaoka, and S.K. Burley Crystal structure of the MazE/MazF complex: Molecular bases of antidote-toxin recognition Mol. Cell 11 2003 875 884
97. I. Marianovsky, E. Aizenman, H. Engelberg-Kulka, and G. Glaser The regulation of the Escherichia coli mazEF promoter involves an unusual alternating palindrome J. Biol. Chem. 276 2001 5975 5984
98. S.K. Khoo, B. Loll, W.T. Chan, R.L. Shoeman, L. Ngoo, C.C. Yeo, and A. Meinhart Molecular and structural characterization of the PezAT chromosomal toxin-antitoxin system of the human pathogen Streptococcus pneumoniae J. Biol. Chem. 282 2007 19606 19618
99. M. Coles, S. Djuranovic, J. Soding, T. Frickey, K. Koretke, V. Truffault, J. Martin, and A.N. Lupas AbrB-like transcription factors assume a swapped hairpin fold that is evolutionarily related to double-psi beta barrels Structure 13 2005 919 928
100. M.J. Mate, R. Vincentelli, N. Foos, D. Raoult, C. Cambillau, and M. Ortiz-Lombardia Crystal structure of the DNA-bound VapBC2 antitoxin/toxin pair from Rickettsia felis Nucleic Acids Res. 40 2012 3245 3258
101. C. Neubauer, Y.G. Gao, K.R. Andersen, C.M. Dunham, A.C. Kelley, J. Hentschel, K. Gerdes, V. Ramakrishnan, and D.E. Brodersen The structural basis for mRNA recognition and cleavage by the ribosome-dependent endonuclease RelE Cell 139 2009 1084 1095
102. M. Overgaard, J. Borch, and K. Gerdes RelB and RelE of Escherichia coli form a tight complex that represses transcription via the ribbon-helix-helix motif in RelB J. Mol. Biol. 394 2009 183 196
103. G.Y. Li, Y. Zhang, M. Inouye, and M. Ikura Structural mechanism of transcriptional autorepression of the Escherichia coli RelB/RelE antitoxin/toxin module J. Mol. Biol. 380 2008 107 119
104. H. Takagi, Y. Kakuta, T. Okada, M. Yao, I. Tanaka, and M. Kimura Crystal structure of archaeal toxin-antitoxin RelE-RelB complex with implications for toxin activity and antitoxin effects Nat. Struct. Mol. Biol. 12 2005 327 331
105. G.Y. Li, Y. Zhang, M. Inouye, and M. Ikura Inhibitory mechanism of E. coli RelE/RelB toxin/antitoxin module involves a helix displacement near a mRNA interferase active site J. Biol. Chem. 284 2009 14628 14636
106. R. Singh, C.E.I.I.I. Barry, and H.I. Boshoff The three RelE homologs of Mycobacterium tuberculosis have individual, drug-specific effects on bacterial antibiotic tolerance J. Bacteriol. 192 2010 1279 1291
107. K.D. Han, S.J. Park, S.B. Jang, W.S. Son, and B.J. Lee Solution structure of conserved hypothetical protein HP0894 from Helicobacter pylori Proteins 61 2005 1111 1113
108. K.D. Han, A. Matsuura, H.C. Ahn, A.R. Kwon, Y.H. Min, H.J. Park, H.S. Won, S.J. Park, D.Y. Kim, and B.J. Lee Functional identification of toxin-antitoxin molecules from Helicobacter pylori 26695 and structural elucidation of the molecular interactions J. Biol. Chem. 286 2011 4842 4853
109. K.D. Han, S.J. Park, S.B. Jang, and B.J. Lee Solution structure of conserved hypothetical protein HP0892 from Helicobacter pylori Proteins 70 2008 599 602
110. I. Cherny, and E. Gazit The YefM antitoxin defines a family of natively unfolded proteins: Implications as a novel antibacterial target J. Biol. Chem. 279 2004 8252 8261
111. B. Kedzierska, L.-Y. Lian, and F. Hayes Toxin-antitoxin regulation: Bimodal interaction of YefM-YoeB with paired DNA palindromes exerts transcriptional autorepression Nucleic Acids Res. 35 2007 325 339
112. C. Nieto, I. Cherny, S.K. Khoo, M.G. Lacoba, W.T. Chan, and C.C. Yeo The yefM-yoeB toxin-antitoxin systems of E. coli and Streptococcus pneumoniae: Functional and structural correlation J. Bacteriol. 189 2007 1266 1278
113. A. Meinhart, J.C. Alonso, N. Sträter, and W. Saenger Crystal structure of the plasmid maintenance system epsilon/zeta: Functional mechanism of toxin zeta and inactivation by epsilon 2 zeta 2 complex formation Proc. Natl. Acad. Sci. U. S. A. 100 2003 1661 1666
114. J.C. DeNap, and P.J. Hergenrother Bacterial death comes full circle: Targeting plasmid replication in drug-resistant bacteria Org. Biomol. Chem. 3 2005 959 966
115. J.J. Williams, and P.J. Hergenrother Exposing plasmids as the Achilles' heel of drug-resistant bacteria Curr. Opin. Chem. Biol. 12 2008 389 399
116. V.S. Lioy, O. Rey, D. Balsa, T. Pellicer, and J.C. Alonso A toxin-antitoxin module as a target for antimicrobial development Plasmid 63 2010 31 39
117. N.Q. Balaban Persistence: Mechanisms for triggering and enhancing phenotypic variability Curr. Opin. Genet. Dev. 21 2011 768 775