Riboswitch-based antibacterial drug discovery using high-throughput screening methods

Expert Opinion on Drug Discovery

Volumn 8, Issue 1, 2013, Pages 65-82

  Penchovsky, Robert ^a   Stoilova, Cvetelina C ^a  

^a UNIVERSITY OF SOFIA   (Bulgaria)

Author keywords

Antibacterial drug discovery; Bacterial riboswitches; Control of gene expression with riboswitches; Riboswitches in bacterial human pathogens; RNA as a target for antibacterial drug discovery

Indexed keywords

ANTIBIOTIC AGENT; BACTERIAL RNA; FLAVINE MONONUCLEOTIDE; FLUORIDE; LYSINE; MESSENGER RNA; PURINE; RIBOFLAVIN;

5' UNTRANSLATED REGION; ALGORITHM; BACILLUS SUBTILIS; BORRELIA BURGDORFERI; CAMPYLOBACTER JEJUNI; CELL FUNCTION; CORYNEBACTERIUM DIPHTHERIAE; DRUG SYNTHESIS; FRANCISELLA TULARENSIS; GENE EXPRESSION REGULATION; HIGH THROUGHPUT SCREENING; IN VITRO STUDY; LEGIONELLA PNEUMOPHILA; LEPTOSPIRA INTERROGANS; LISTERIA MONOCYTOGENES; MYCOBACTERIUM LEPRAE; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; OPERON; PRIORITY JOURNAL; PSEUDOMONAS AERUGINOSA; REVIEW; RIBOSWITCH; RNA ANALYSIS; RNA BINDING; SALMONELLA TYPHI; STREPTOCOCCUS AGALACTIAE; VIBRIO CHOLERAE; YERSINIA PESTIS;

ANIMALS; DRUG DISCOVERY; GENE EXPRESSION REGULATION, BACTERIAL; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; RIBOSWITCH; RNA, BACTERIAL; RNA, MESSENGER;

EID: 84871549196     PISSN: 17460441     EISSN: 1746045X     Source Type: Journal    
DOI: 10.1517/17460441.2013.740455     Document Type: Review

References (73)

1. Theuretzbacher U, Toney JH. Nature's clarion call of antibacterial resistance: are we listening? Curr Opin Investig Drugs 2006;7:158-66
2. Blount KF, Breaker RR. Riboswitches as antibacterial drug targets. Nat Biotechnol 2006;24:1558-64
3. Deigan KE, Ferre-D'Amare AR. Riboswitches: discovery of drugs that target bacterial gene-regulatory RNAs. Acc Chem Res 2011;44:1329-38
4. Tucker BJ, Breaker RR. Riboswitches as versatile gene control elements. Curr Opin Struct Biol 2005;15:342-8
5. Mandal M, Breaker RR. Gene regulation by riboswitches. Nat Rev Mol Cell Biol 2004;5:451-63
6. Penchovsky R, Breaker RR. Computational design and experimental validation of oligonucleotide-sensing allosteric ribozymes. Nat Biotechnol 2005;23:1424-33
7. Penchovsky R. Engineering integrated digital circuits with allosteric ribozymes for scaling up molecular computation and diagnostics. ACS Synthetic Biol 2012;1(10):471-82
8. Isaacs FJ, Dwyer DJ, Collins JJ. RNA synthetic biology. Nat Biotechnol 2006;24:545-54
9. Penchovsky R. Engineering gene control circuits with allosteric ribozymes in human cells as a medicine of the future. Quality assurance in healthcare service delivery, nursing and personalized medicine: technologies and processes. 2012; DOI: 10.4018/978-1-61350-120-7. ch005, 71-92
10. Otani S, Takatsu M, Nakano M, et al. Letter: roseoflavin, a new antimicrobial pigment from Streptomyces. J Antibiot (Tokyo) 1974;27:86-7
11. Ramesh A, Winkler WC. Magnesium-sensing riboswitches in bacteria. RNA Biol 2010;7:77-83
12. Baker JL, Sudarsan N, Weinberg Z, et al. Widespread genetic switches and toxicity resistance proteins for fluoride. Science 2012;335:233-5
13. Cheah MT, Wachter A, Sudarsan N, Breaker RR. Control of alternative RNA splicing and gene expression by eukaryotic riboswitches. Nature 2007;447:497-500
14. Wachter A, Tunc-Ozdemir M, Grove BC, et al. Riboswitch control of gene expression in plants by splicing and alternative 3' end processing of mRNAs. Plant Cell 2007;19:3437-50
15. Bocobza S, Adato A, Mandel T, et al. Riboswitch-dependent gene regulation and its evolution in the plant kingdom. Genes Dev 2007;21:2874-9
16. Breaker RR. Complex riboswitches. Science 2008;319:1795-7
17. Mandal M, Lee M, Barrick JE, et al. A glycine-dependent riboswitch that uses cooperative binding to control gene expression. Science 2004;306:275-9
18. Loh E, Dussurget O, Gripenland J, et al. A trans-acting riboswitch controls expression of the virulence regulator PrfA in Listeria monocytogenes. Cell 2009;139:770-9
19. Bastet L, Dube A, Masse E, Lafontaine DA. New insights into riboswitch regulation mechanisms. Mol Microbiol 2011;80:1148-54
20. Kazanov MD, Vitreschak AG, Gelfand MS. Abundance and functional diversity of riboswitches in microbial communities. BMC Genomics 2007;8:347
21. Joyce GF. Forty years of in vitro evolution. Angew Chem Int Ed Engl 2007;46:6420-36
22. Famulok M, Mayer G. Chemical biology: aptamers in nanoland. Nature 2006;439:666-9
23. Winkler WC, Breaker RR. Regulation of bacterial gene expression by riboswitches. Annu Rev Microbiol 2005;59:487-517
24. Zhang J, Lau MW, Ferre-D'Amare AR. Ribozymes and riboswitches: modulation of RNA function by small molecules. Biochemistry 2010;49:9123-31
25. Mandal M, Breaker RR. Adenine riboswitches and gene activation by disruption of a transcription terminator. Nat Struct Mol Biol 2004;11:29-35
26. Hollands K, Proshkin S, Sklyarova S, et al. Riboswitch control of Rho-dependent transcription termination. Proc Natl Acad Sci USA 2012;109:5376-81
27. Winkler WC, Nahvi A, Roth A, et al. Control of gene expression by a natural metabolite-responsive ribozyme. Nature 2004;428:281-6
28. Winkler WC, Cohen-Chalamish S, Breaker RR. An mRNA structure that controls gene expression by binding FMN. Proc Natl Acad Sci USA 2002;99:15908-13
29. Gelfand MS, Mironov AA, Jomantas J, et al. A conserved RNA structure element involved in the regulation of bacterial riboflavin synthesis genes. Trends Genet 1999;15:439-42
30. Lee ER, Blount KF, Breaker RR. Roseoflavin is a natural antibacterial compound that binds to FMN riboswitches and regulates gene expression. RNA Biol 2009;6:187-94
31. Mansjo M, Johansson J. The riboflavin analog roseoflavin targets an FMN-riboswitch and blocks Listeria monocytogenes growth, but also stimulates virulence gene-expression and infection. RNA Biol 2011;8:674-80
32. Blount K, Puskarz I, Penchovsky R, Breaker R. Development and application of a high-throughput assay for glmS riboswitch activators. RNA Biol 2006;3:77-81
33. Klein DJ, Ferre-D'Amare AR. Structural basis of glmS ribozyme activation by glucosamine-6-phosphate. Science 2006;313:1752-6
34. Klein DJ, Wilkinson SR, Been MD, Ferre-D'Amare AR. Requirement of helix P2.2 and nucleotide G1 for positioning the cleavage site and cofactor of the glmS ribozyme. J Mol Biol 2007;373:178-89
35. Ott E, Stolz J, Lehmann M, Mack M. The RFN riboswitch of Bacillus subtilis is a target for the antibiotic roseoflavin produced by Streptomyces davawensis. RNA Biol 2009;6:276-80
36. Lu Y, Chen NY, Paulus H. Identification of aecA mutations in Bacillus subtilis as nucleotide substitutions in the untranslated leader region of the aspartokinase II operon. J Gen Microbiol 1991;137:1135-43
37. Blount KF, Wang JX, Lim J, et al. Antibacterial lysine analogs that target lysine riboswitches. Nat Chem Biol 2007;3:44-9
38. Sudarsan N, Wickiser JK, Nakamura S, et al. An mRNA structure in bacteria that controls gene expression by binding lysine. Genes Dev 2003;17:2688-97
39. Di Girolamo A, Di Girolamo M, Cini C, et al. Thialysine utilization by thialysine resistant CHO cells. Physiol Chem Phys Med NMR 1986;18:33-6
40. Sudarsan N, Cohen-Chalamish S, Nakamura S, et al. Thiamine pyrophosphate riboswitches are targets for the antimicrobial compound pyrithiamine. Chem Biol 2005;12:1325-35
41. Robbins WJ. The pyridine analog of thiamin and the growth of fungi. Proc Natl Acad Sci USA 1941;27:419-22
42. Iwashima A, Wakabayashi Y, Nose Y. Formation of pyrithiamine pyrophosphate in brain tissue. J Biochem 1976;79:845-7
43. Thore S, Frick C, Ban N. Structural basis of thiamine pyrophosphate analogues binding to the eukaryotic riboswitch. J Am Chem Soc 2008;130:8116-17
44. Edwards TE, Ferre-D'Amare AR. Crystal structures of the thi-box riboswitch bound to thiamine pyrophosphate analogs reveal adaptive RNA-small molecule recognition. Structure 2006;14:1459-68
45. Thomas JR, Hergenrother PJ. Targeting RNA with small molecules. Chem Rev 2008;108:1171-224
46. Lunse CE, Schmidt MS, Wittmann V, Mayer G. Carba-sugars activate the glmS-riboswitch of Staphylococcus aureus. ACS Chem Biol 2011;6:675-8
47. Mayer G, Famulok M. High-throughput-compatible assay for glmS riboswitch metabolite dependence. ChemBioChem 2006;7:602-4
48. Penchovsky R. Computational design and experimental validation of small molecule-sensing allosteric ribozymes. under review
49. Scott WG. Crystallographic analyses of chemically synthesized modified hammerhead RNA sequences as a general approach toward understanding ribozyme structure and function. Methods Mol Biol 1997;74:387-91
50. Wang JY, Qiu L, Drlica K. Hammerhead ribozyme structure probed by cell extracts. Gene 1996;181:117-20
51. Flores R, Hernandez C, de la Pena M, et al. Hammerhead ribozyme structure and function in plant RNA replication. Methods Enzymol 2001;341:540-52
52. Penchovsky R. High-throughput compatible beads-based array for transcription termination of FMN riboswitch. Under review
53. Wickiser JK, Winkler WC, Breaker RR, Crothers DM. The speed of RNA transcription and metabolite binding kinetics operate an FMN riboswitch. Mol Cell 2005;18:49-60
54. Penchovsky R, Birch-Hirschfeld E, McCaskill JS. End-specific covalent photo-dependent immobilisation of synthetic DNA to paramagnetic beads. Nucleic Acids Res 2000;28:E98
55. Kim JN, Blount KF, Puskarz I, et al. Design and antimicrobial action of purine analogues that bind Guanine riboswitches. ACS Chem Biol 2009;4:915-27
56. Watson PY, Fedor MJ. The glmS riboswitch integrates signals from activating and inhibitory metabolites in vivo. Nat Struct Mol Biol 2011;18:359-63
57. Anderson PC, Mecozzi S. Unusually short RNA sequences: design of a 13-mer RNA that selectively binds and recognizes theophylline. J Am Chem Soc 2005;127:5290-1
58. Subramaniam S, Mehrotra M, Gupta D. Virtual high throughput screening (vHTS)-a perspective. Bioinformation 2008;3:14-17
59. Cheatham TE III, Young MA. Molecular dynamics simulation of nucleic acids: successes, limitations, and promise. Biopolymers 2000;56:232-56
60. Rabinowitz JR, Goldsmith MR, Little SB, Pasquinelli MA. Computational molecular modeling for evaluating the toxicity of environmental chemicals: prioritizing bioassay requirements. Environ Health Perspect 2008;116:573-7
61. Lang PT, Brozell SR, Mukherjee S, et al. DOCK 6: combining techniques to model RNA-small molecule complexes. RNA 2009;15:1219-30
62. Sutcliffe JA. Improving on nature: antibiotics that target the ribosome. Curr Opin Microbiol 2005;8:534-42
63. Blount KF, Zhao F, Hermann T, Tor Y. Conformational constraint as a means for understanding RNA-aminoglycoside specificity. J Am Chem Soc 2005;127:9818-29
64. Faber C, Sticht H, Schweimer K, Rosch P. Structural rearrangements of HIV-1 Tat-responsive RNA upon binding of neomycin B. J Biol Chem 2000;275:20660-6
65. Kirk SR, Tor Y. tRNA(Phe) binds aminoglycoside antibiotics. Bioorg Med Chem 1999;7:1979-91
66. Kirk SR, Luedtke NW, Tor Y. 2-Aminopurine as a real-time probe of enzymatic cleavage and inhibition of hammerhead ribozymes. Bioorg Med Chem 2001;9:2295-301
67. Kumar S, Arya DP. Recognition of HIV TAR RNA by triazole linked neomycin dimers. Bioorg Med Chem Lett 2011;21:4788-92
68. Ataide SF, Wilson SN, Dang S, et al. Mechanisms of resistance to an amino acid antibiotic that targets translation. ACS Chem Biol 2007;2:819-27
69. Koedam JC. The mode of action of pyrithiamine as an inductor of thiamine deficiency. Biochim Biophys Acta 1958;29:333-44
70. Serganov A, Polonskaia A, Phan AT, et al. Structural basis for gene regulation by a thiamine pyrophosphate-sensing riboswitch. Nature 2006;441:1167-71
71. Thore S, Leibundgut M, Ban N. Structure of the eukaryotic thiamine pyrophosphate riboswitch with its regulatory ligand. Science 2006;312:1208-11
72. Mandal M, Boese B, Barrick JE, et al. Riboswitches control fundamental biochemical pathways in Bacillus subtilis and other bacteria. Cell 2003;113:577-86
73. Haas AL, Laun NP, Begley TP. Thi20, a remarkable enzyme from Saccharomyces cerevisiae with dual thiamin biosynthetic and degradation activities. Bioorg Chem 2005;33:338-44