Riboswitches as antibacterial drug targets

Nature Biotechnology

Volumn 24, Issue 12, 2006, Pages 1558-1564

  Blount, Kenneth F ^a   Breaker, Ronald R ^a  

^a YALE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBIOTICS; DRUG DOSAGE; DRUG THERAPY; ENCODING (SYMBOLS); GENETIC ENGINEERING; METABOLITES;

ANTIBACTERIAL DRUG TARGETS; METABOLITE BINDING; RIBOSWITCHES;

RNA;

AMINOETHYLCYSTEINE; ANTIINFECTIVE AGENT; DEXTRO 4 OXALYSINE; DRUG METABOLITE; FLUDARABINE; LYSINE DERIVATIVE; MESSENGER RNA; PYRITHIAMINE; PYRITHIAMINE PYRROPHOSPHATE; RIBOFLAVIN; ROSEOFLAVIN; THIAMINE;

ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; BACTERICIDAL ACTIVITY; BACTERIUM; DRUG DESIGN; DRUG PROTEIN BINDING; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG TARGETING; GENE CONTROL; GENE EXPRESSION; GENE REPRESSION; HIGH THROUGHPUT SCREENING; NONHUMAN; PRIORITY JOURNAL; PROTEIN STRUCTURE; REVIEW; RIBOSWITCH;

ANTI-BACTERIAL AGENTS; APTAMERS, NUCLEOTIDE; DRUG DESIGN; GENE EXPRESSION REGULATION, BACTERIAL; REGULATORY SEQUENCES, RIBONUCLEIC ACID; RNA, MESSENGER;

EID: 33845700514     PISSN: 10870156     EISSN: 15461696     Source Type: Journal    
DOI: 10.1038/nbt1268     Document Type: Review

References (63)

1. Theuretzbacher, U. & Toney, J.H. Nature's clarion call of antibacterial resistance: are we listening? Curr. Opin. Investig. Drugs 7, 158-166 (2006).
2. D'Costa, V.M., McGrann, K.M., Hughes, D.W. & Wright, G.D. Sampling the antibiotic resistome. Science 311, 374-377 (2006).
3. Mandal, M. & Breaker, R.R. Gene regulation by riboswitches. Nat. Rev. Mol. Cell Biol. 5, 451-463 (2004).
4. Tucker, B.J. & Breaker, R.R. Riboswitches as versatile gene control elements. Curr. Opin. Struct. Biol. 15, 342-348 (2005).
5. Winkler, W.C. & Breaker, R.R. Regulation of bacterial gene expression by riboswitches. Annu. Rev. Microbiol. 59, 487-517 (2005).
6. Winkler, W., Nahvi, A. & Breaker, R.R. Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression. Nature 419, 952-956 (2002).
7. Rodionov, D.A., Vitreschak, A.G., Mironov, A.A. & Gelfand, M.S. Comparative genomics of thiamin biosynthesis in procaryotes. New genes and regulatory mechanisms. J. Biol. Chem. 277, 48949-48959 (2002).
8. Sudarsan, N., Barrick, J.E. & Breaker, R.R. Metabolite-binding RNA domains are present in the genes of eukaryotes. RNA 9, 644-647 (2003).
9. Sudarsan, N., Cohen-Chalamish, S., Nakamura, S., Emilsson G.M. & Breaker, R.R. Thiamine pyrophosphate riboswitches are targets for the antimicrobial compound pyrithiamine. Chem. Biol. 12, 1325-1335 (2005).
10. Zhang, R., Ou, H.-Y. & Zhang, C.-T. DEG, a database of essential genes. Nucleic Acids Res. 32, D271-D272 (2004).
11. Forsyth, R.A. et al. A genome-wide strategy for the identification of essential genes in Staphylococcus aureus. Mol. Microbiol. 43, 1387-1400 (2002).
12. Dunman, P.M. et al. Transcription profiling-based identification of Staphylococcus aureus genes regulated by the agr and/or sarA loci. J. Bacteriol. 183, 7341-7353 (2001).
13. Epshtein, V., Mironov, A.S. & Nudler, E. The riboswitch-mediated control of sulfur metabolism in bacteria. Proc. Natl. Acad. Sci. USA 100, 5052-5056 (2003).
14. Murphy, B.A., Grundy, F.J. & Henkin, T.M. Prediction of gene function in methylthioadenosine recycling from regulatory signals. J. Bacteriol. 184, 2314-2318 (2002).
15. Winkler, W.C., Nahvi, A., Sudarsan, N., Barrick, J.E. & Breaker, R.R. An mRNA structure that controls gene expression by binding S- adenosylmethionine. Nat. Struct. Biol. 10, 701-707 (2003).
16. 12 riboswitches are widespread genetic control elements in prokaryotes. Nucleic Acids Res. 32, 143-150 (2004).
17. Monaghan, R.L. & Barrett, J.F. Antibacterial drug discovery-then, now and the genomics future. Biochem. Pharmacol. 71, 901-909 (2006).
18. Knowles, D.J., Foloppe, N., Matassova, N.B. & Murchie, A.I. The bacterial ribosome, a promising focus for structure-based drug design. Curr. Opin. Pharmacol. 2, 501-506 (2002).
19. Steitz, T.A. On the structural basis of peptide-bond formation and antibiotic resistance from atomic structures of the large ribosomal subunit. FEBS Lett. 579, 955-958 (2005).
20. Zaman, G.J.R. & Michiels, P.J.A. Targeting RNA with small molecule drugs in Trends in RNA Research (ed. McNamara, P.) 1-21 (Nova Science Publishers, Inc., Hauppauge, NY, 2006).
21. Hermann, T. & Tor, Y. RNA as a target for small-molecule therapeutics. Expert. Opin. Ther. Pat. 15, 49-62 (2005).
22. Mandal, M., Boese, B., Barrick, J.E., Winkler, W.C. & Breaker, R.R. Riboswitches control fundamental biochemical pathways in Bacillus subtilis and other bacteria. Cell 113, 577-586 (2003).
23. Serganov, A. et al. Structural basis for discriminative regulation of gene expression by adenine- and guanine-sensing mRNAs. Chem. Biol. 11, 1729-1741 (2004).
24. Batey, R.T., Gilbert, S.D. & Montange, R.K. Structure of a natural guanine-responsive riboswitch complexed with the metabolite hypoxanthine. Nature 432, 411-415 (2004).
25. Serganov, A., Polonskaia, A., Phan, A.T., Breaker, R.R. & Patel, D.J. Structural basis for gene regulation by a thiamine pyrophosphate-sensing riboswitch. Nature 441, 1167-1171 (2006).
26. Thore, S., Leibundgut, M. & Ban, N. Structure of the eukaryotic thiamine pyrophosphate riboswitch with its regulatory ligand. Science 312, 1208-1211 (2006).
27. Montange, R.K. & Batey, R.T. Structure of the S-adenosylmethionine riboswitch regulatory mRNA element. Nature 441, 1172-1175 (2006).
28. Lim, J., Winkler, W.C., Nakamura, S., Scott, V. & Breaker, R.R. Molecular-recognition characteristics of SAM-binding riboswitches. Angew. Chem. Int. Edn Engl. 45, 964-968 (2006).
29. Robbins, W.J. The pyridine analog of thiamine and the growth of fungi. Proc. Natl. Acad. Sci. USA 27, 419-422 (1941).
30. Woolley, D.W. & White, A.G.C. Selective reversible inhibition of microbial growth with pyrithiamine. J. Exp. Med. 78, 489-497 (1943).
31. Iwashima, A., Wakabayashi, Y. & Nose, Y. Formation of thiamine pyrophosphate in brain tissue. J. Biochem. 79, 845-847 (1976).
32. Shiota, T., Folk, J.E. & Tietze, F. Inhibition of lysine utilization in bacteria by S-(beta-aminoethyl) cysteine and its reversal by lysine peptides. Arch. Biochem. Biophys. 77, 372-377 (1958).
33. McCord, T., Ravel, J., Skinner, C. & Shive, W. DL-4-oxalysine, an inhibitory analog of lysine. J. Am. Chem. Soc. 79, 5693-5696 (1957).
34. Blount, K.F., Wang, X.J., Lim, J., Sudarsan, N. & Breaker, R.R. Antibacterial compounds that target lysine riboswitches. Nat. Chem. Biol. in the press (2007).
35. Sudarsan, N., Wickiser, J.K., Nakamura, S., Ebert, M.S. & Breaker, R.R. An mRNA structure in bacteria that controls gene expression by binding lysine. Genes Dev. 17, 2688-2697 (2003).
36. Vold, B., Szulmajster, J. & Carbone, A. Regulation of dihydropicolinate synthase and aspartate kinase in Bacillus subtilis. J. Bacteriol. 121, 970-974 (1975).
37. Lu, Y., Shevtchenko, T. & Paulus, H. Fine structure mapping of cis-acting control sites in the lysC operon of Bacillus subtilis. FEMS Microbiol. Lett. 71, 23-27 (1992).
38. Matsui, K. et al. Riboflavin production by roseoflavin-resistant strains of some bacteria. Agric. Biol. Chem. 46, 2003-2008 (1982).
39. Berezovskii, V.M., Stepanov, A.I., Polyakova, N.A., Tulchinskaya, L.S. & Kukanova, A.Y. Studies of a group of allo- and isoallxazine. XLVI. Synthesis and biological specificity of amino analogs. Bioorg. Khim, 3, 521-524 (1977).
40. Gelfand, M.S., Mironov, A.A., Jomantas, J., Kozlov, Y.I. & Perumov, D.A. A conserved RNA structure element involved in the regulation of bacterial riboflavin synthesis genes. Trends Genet. 15, 439-442 (1999).
41. Winkler, W.C., Cohen-Chalamish, S. & Breaker, R.R. An mRNA structure that controls gene expression by binding FMN. Proc. Natl. Acad. Sci. USA 99, 15908-15913 (2002).
42. Burgess, C., O'Connel-Motherway, M., Sybesma, W., Hugenholtz, J. & van Sinderen, D. Riboflavin production in Lactococcus lactis: potential for in situ production of vitamin-enriched foods. Appl. Environ. Microbiol. 70, 5769-5777 (2004).
43. Kreneva, R.A. & Perumov, D.A. Genetic mapping of regulatory mutations of Bacillus subtilis riboflavin operon. Mol. Gen. Genet. 222, 467-469 (1990).
44. Kil, Y.V., Mironov, V.N., Gorishin, I., Kreneva, R.A. & Perumov, D.A. Riboflavin operon of Bacillus subtilis: unusual symmetric arrangement of the regulatory region. Mol. Gen. Genet. 233, 483-486 (1992).
45. Edwards, T.E. & Ferré-D'Amaré, A.R. Crystal structures of the thi-box riboswitch bound to thiamine pyrophosphate analogs reveal adaptive RNA-small molecule recognition. Structure 14, 1459-1468 (2006).
46. Winkler, W.C., Nahvi, A., Roth, A., Collins, J.A. & Breaker, R.R. Control of gene expression by a natural metabolite-responsive ribozyme. Nature 428, 281-286 (2004).
47. Mayer, G. & Famulok, M. High-throughput-compatible assay for glmS riboswitch metabolite dependence. ChemBioChem 7, 602-604 (2006).
48. Blount, K.F., Puskarz, I., Penchovsky, R. & Breaker, R.R. Development and application of a high-throughput assay for glmS riboswitch activators. RNA Biology 3, 77-81 (2006).
49. Seetharaman, S., Zivarts, M., Sudarsan, N. & Breaker, R.R. Immobilized RNA switches for the analysis of complex chemical and biological mixtures. Nat. Biotechnol. 19, 336-341 (2001).
50. Sudarsan, N., Hammond, M.C., Block, K., Welz, R. & Breaker, R.R. Tandem riboswitch architectures exhibit complex gene control functions. Science 314, 300-304 (2006).
51. Lee, J.-M. et al. RNA expression analysis using an antisense Bacillus subtilis genome array. J. Bacteriol. 183, 7371-7380 (2001).
52. Rodionov, D.A., Vitreschak, A.G., Mironov, A.A. & Gelfand, M.S. Regulation of lysine biosynthesis and transport genes in bacteria: yet another RNA riboswitch? Nucleic Acids Res. 31, 6748-6757 (2003).
53. 2 (riboflavin). Annu. Rev. Nutr. 20, 153-167 (2000).
54. Wickiser, J.K., Winkler, W.C., Breaker, R.R. & Crothers, D.M. The speed of RNA transcription and metabolite binding kinetics operate an FMN riboswitch. Mol. Cell 18, 49-60 (2005).
55. Wickiser, J.K., Cheah, M.T., Breaker, R.R. & Crothers, D.M. The kinetics of ligand binding by an adenine-sensing riboswitch. Biochemistry 44, 13404-13414 (2005).
56. Koedam, J.C. The mode of action of pyrithiamine as an inducer of thiamine deficiency. Biochim. Biophys. Acta 29, 333-344 (1958).
57. Di Girolamo, M., Di Girolamo, A., Cini, C., Coccia, R. & De Marco, C. Thialysine utilization for protein synthesis by CHO cells. Physiol. Chem. Phys. Med. NMR 18, 159-164 (1986).
58. Saxild, H.H. & Nygaard, P. Genetic and physiological characterization of Bacillus subtilis mutants resistant to purine analogs. J. Bacteriol. 169, 2977-2983 (1987).
59. Haas, A.L., Laun, N.P. & Begley, T.P. Thi20, a remarkable enzyme from Saccharomyces cerevisiae with dual thiamine biosynthetic and degradation activities. Bioorg. Chem. 33, 338-344 (2005).
60. McDaniel, B.A., Grundy, F.J., Kurlekar, V.P., Tomsic, J. & Henkin, T.M. Identification of a mutation in the Bacillus subtilis S-adenosylmethionine synthetase gene that results in derepression of S-box gene expression. J. Bacteriol. 188, 3674-3681 (2006).
61. Barrick, J.E. et al. New RNA motifs suggest an expanded scope for riboswitches in bacterial genetic control. Proc. Natl. Acad. Sci. USA 101, 6421-6426 (2004).
62. Corbino, K.A. et al. Evidence for a second class of S-adenosylmethionine riboswitches and other regulatory RNA motifs in alpha-proteobacteria. Genome Biol. 6, R70.1-R70.10 (2005).
63. Mandal, M. et al. A glycine-dependent riboswitch that uses cooperative binding to control gene expression. Science 306, 275-279 (2004).