Renaissance in antibiotic discovery: Some novel approaches for finding drugs to treat bad bugs

Current Medicinal Chemistry

Volumn 22, Issue 18, 2015, Pages 2140-2158

  Gadakh, Bharat ^a   Van Aerschot, Arthur ^a  

^a REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

Author keywords

Acylated homoserine lactone; Antibiotic discovery; Antibiotics; Antivirulence strategy; Autoinducers; Bacteriophages; Genomic approach; Non multiplying bacteria; Phage therapy; Quorum sensing; Resistance; Screening strategies; Structure based drug design.

Indexed keywords

ANTIBIOTIC AGENT; BACTERIAL ENZYME; DELAMANID; DIAMINE; DIHYDROFOLATE REDUCTASE; NITROIMIDAZOLE; PRETOMANID; SULFAMETHOXAZOLE; TRIMETHOPRIM; VIRULENCE FACTOR; ANTIINFECTIVE AGENT;

ANTIBACTERIAL ACTIVITY; BACTERIAL GENOME; BEDBUG BITE; CELL COMMUNICATION; CELL MOTILITY; CLINICAL TRIAL (TOPIC); DNA BINDING; DRUG DESIGN; DRUG SENSITIVITY; ENERGY METABOLISM; ENZYMATIC DEGRADATION; GENE CLUSTER; GENOMICS; HIGH THROUGHPUT SCREENING; HUMAN; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; PHASE 3 CLINICAL TRIAL (TOPIC); QUORUM SENSING; REVIEW; SIGNAL TRANSDUCTION; STRUCTURE BASED DRUG DESIGN; TRANSCRIPTION INITIATION; X RAY CRYSTALLOGRAPHY; ANTIBIOTIC RESISTANCE; BACTERIUM; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DEVELOPMENT; DRUG EFFECTS; MICROBIAL SENSITIVITY TEST;

ANTI-BACTERIAL AGENTS; BACTERIA; DRUG DISCOVERY; DRUG RESISTANCE, BACTERIAL; MICROBIAL SENSITIVITY TESTS; MOLECULAR STRUCTURE;

EID: 84934300696     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/0929867322666150319115828     Document Type: Review

References (151)

1. Coates, A.R.; Hu, Y. Novel approaches to developing new antibiotics for bacterial infections. Br. J. Pharmacol., 2007, 152, 1147-1154.
2. Brotz-Oesterhelt, H.; Sass, P. Postgenomic strategies in antibacterial drug discovery. Future Microbiol., 2010, 5, 1553-1579.
3. Fakuda, Y. New approaches to overcoming bacterial resistance. Drugs Fut., 2009, 34, 127-136.
4. Bockstael, K.; Van Aerschot, A. Antimicrobial resistance in bacteria. Cent. Eur. J. Med., 2009, 4, 141-155.
5. Charifson, P.S.; Grossman, T.H.; Mueller, P. The use of structure-guided design to discover new anti-microbial agents: focus on antibacterial resistance. Anti-Infect. Agents Med. Chem., 2009, 8, 73-86.
6. Projan, S.J.; Bradford, P.A. Late stage antibacterial drugs in the clinical pipeline. Curr. Opin. Microbiol., 2007, 10, 441-446.
7. Katz, M.L.; Mueller, L.V.; Polyakov, M.; Weinstock, S.F. Where have all the antibiotic patents gone? Nat. Biotech., 2006, 24, 1529-1531.
8. Talbot, G.H.; Bradley, J.; Edwards, J.E.; Gilbert, D.; Scheld, M.; Bartlett, J.G. Bad bugs need drugs: An update on the development pipeline from the antimicrobial availability task force of the infectious diseases society of America. Clin. Infect. Dis., 2006, 42, 657-668.
9. Simmons, K.J.; Chopra, I.; Fishwick, C.W.G. Structure-based discovery of antibacterial drugs. Nat. Rev. Microbiol., 2010, 8, 501-510.
10. Overbye, K.M.; Barrett, J.F. Antibiotics: Where did we go wrong? Drug Discov. Today, 2005, 10, 45-52.
11. Senior, M. Sovaldi makes blockbuster history, ignites drug pricing unrest. Nat. Biotech., 2014, 32, (6), 501-502.
12. Kroll, D., Antibiotic pipeline revival: FDA approves Cubist Pharmaceuticals' sivextro for MRSA, other serious skin infections. Forbes 2014.
13. Edson, J.A.; Kwon, Y.J. RNAi for silencing drug resistance in microbes toward development of nanoantibiotics. J. Control. Release, 2014, 189, 150-157.
14. Brogden, K.A. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat. Rev. Microbiol., 2005, 3, 238-250.
15. Pushpanathan, M.; Gunasekaran, P.; Rajendhran, J. Antimicrobial peptides: Versatile biological properties. Int. J. Peptides, 2013, 2013, 15.
16. Payne, D.J.; Gwynn, M.N.; Holmes, D.J.; Pompliano, D.L. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat. Rev. Drug Discov., 2007, 6, 29-40.
17. Gwynn, M.N.; Portnoy, A.; Rittenhouse, S.F.; Payne, D.J. Challenges of antibacterial discovery revisited. Ann. N. Y. Acad. Sci., 2010, 1213, 5-19.
18. Lewis, K. Platforms for antibiotic discovery. Nat. Rev. Drug Discov., 2013, 12, 371-387.
19. Isaacson, R.E. Novel targets for antibiotics. Expert Opin. Invest. Drugs, 1994, 3, 83-91.
20. Coates, A.; Hu, Y.; Bax, R.; Page, C. The future challenges facing the development of new antimicrobial drugs. Nat. Rev. Drug Discov., 2002, 1, 895-910.
21. Barker, J.J. Antibacterial drug discovery and structure-based design. Drug Discov. Today, 2006, 11, 391-404.
22. Anderson, A.C. The process of structure-based drug design. Chem. Biol., 2003, 10, 787-797.
23. Congreve, M.; Murray, C.W.; Blundell, T.L. Keynote review: structural biology and drug discovery. Drug Discov. Today, 2005, 10, 895-907.
24. Kompis, I.M.; Islam, K.; Then, R.L. DNA and RNA synthesis: antifolates. Chem. Rev., 2005, 105, 593-620.
25. Canton, R.; Loza, E.; Morosini, M.I.; Baquero, F. Antimicrobial resistance amongst isolates of Streptococcus pyogenes and Staphylococcus aureus in the PROTEKT antimicrobial surveillance programme during 1999-2000. J. Antimicrob. Chemother., 2002, 50, 9-24.
26. Vickers, A.A.; Potter, N.J.; Fishwick, C.W.G.; Chopra, I.; O' Neill, A.J. Analysis of mutational resistance to trimethoprim in Staphylococcus aureus by genetic and structural modelling techniques. J. Antimicrob. Chemother., 2009, 63, 1112-1117.
27. Summerfield, R.L.; Daigle, D.M.; Mayer, S.; Mallik, D.; Hughes, D.W.; Jackson, S.G.; Sulek, M.; Organ, M.G.; Brown, E.D.; Junop, M.S. A 2.13 Ã structure of E. coli dihydrofolate reductase bound to a novel competitive inhibitor reveals a new binding surface involving the m20 loop region. J. Med. Chem., 2006, 49, 6977-6986.
28. Hawser, S.; Lociuro, S.; Islam, K. Dihydrofolate reductase inhibitors as antibacterial agents. Biochem. Pharmacol., 2006, 71, 941-948.
29. Krievins, D.; Brandt, R.; Hawser, S.; Hadvary, P.; Islam, K. Multicenter, randomized study of the efficacy and safety of intravenous iclaprim in complicated skin and skin structure infections. Antimicrob. Agents Chemother., 2009, 53, 2834-2840.
30. Breukink, E.; de Kruijff, B. Lipid II as a target for antibiotics. Nat. Rev. Drug Discov., 2006, 5, 321-323.
31. Leeuw, E.d.; Li, C.; Zeng, P.; Li, C.; Buin, M.D.-d.; Lu, W.-Y.; Breukink, E.; Lu, W. Functional interaction of human neutrophil peptide-1 with the cell wall precursor lipid II. FEBS Lett., 584, 1543-1548.
32. Varney, K.M.; Bonvin, A.M.J.J.; Pazgier, M.; Malin, J.; Yu, W.; Ateh, E.; Oashi, T.; Lu, W.; Huang, J.; Diepeveen-de Buin, M.; Bryant, J.; Breukink, E.; MacKerell, A.D., Jr.; de Leeuw, E.P.H. Turning defense into offense: Defensin mimetics as novel antibiotics targeting Lipid II. PLoS Pathog., 2013, 9, e1003732.
33. de Leeuw, E.P. Efficacy of the small molecule inhibitor of Lipid II BAS00127538 against Acinetobacter baumannii. Drug Des. Devel. Ther., 2014, 8, 1061.
34. Teng, M.; Hilgers, M.T.; Cunningham, M.L.; Borchardt, A.; Locke, J.B.; Abraham, S.; Haley, G.; Kwan, B.P.; Hall, C.; Hough, G.W.; Shaw, K.J.; Finn, J. Identification of bacteria-selective threonyl-tRNA synthetase substrate inhibitors by structure-based design. J. Med. Chem., 2013, 56, 1748-1760.
35. Tari, L.W.; Li, X.; Trzoss, M.; Bensen, D.C.; Chen, Z.; Lam, T.; Zhang, J.; Lee, S.J.; Hough, G.; Phillipson, D.; Akers-Rodriguez, S.; Cunningham, M.L.; Kwan, B.P.; Nelson, K.J.; Castellano, A.; Locke, J.B.; Brown-Driver, V.; Murphy, T.M.; Ong, V.S.; Pillar, C.M.; Shinabarger, D.L.; Nix, J.; Lightstone, F.C.; Wong, S.E.; Nguyen, T.B.; Shaw, K.J.; Finn, J. Tricyclic GyrB/pare (TriBE) inhibitors: A new class of broad-spectrum dual-targeting antibacterial agents. PLoS ONE, 2013, 8, e84409.
36. Shirude, P.S.; Madhavapeddi, P.; Tucker, J.A.; Murugan, K.; Patil, V.; Basavarajappa, H.; Raichurkar, A.V.; Humnabadkar, V.; Hussein, S.; Sharma, S.; Ramya, V.K.; Narayan, C.B.; Balganesh, T.S.; Sambandamurthy, V.K. Aminopyrazinamides: novel and specific GyrB inhibitors that kill replicating and nonreplicating Mycobacterium tuberculosis. ACS Chem. Biol., 2013, 8, 519-523.
37. Liang, X.; Lee, C.J.; Zhao, J.; Toone, E.J.; Zhou, P. Synthesis, structure, and antibiotic activity of aryl-substituted Lpxc inhibitors. J. Med. Chem., 2013, 56, 6954-6966.
38. Koh, C.Y.; Kim, J.E.; Wetzel, A.B.; de van der Schueren, W.J.; Shibata, S.; Ranade, R.M.; Liu, J.; Zhang, Z.; Gillespie, J.R.; Buckner, F.S.; Verlinde, C.L.; Fan, E.; Hol, W.G. Structures of Trypanosoma brucei methionyl-tRNA synthetase with urea-based inhibitors provide guidance for drug design against sleeping sickness. PLoS Negl. Trop. Dis., 2014, 8, e2775.
39. Venkatesan, A.M.; Agarwal, A.; Abe, T.; Ushirogochi, H.; Yamamura, I.; Ado, M.; Tsuyoshi, T.; Dos Santos, O.; Gu, Y.; Sum, F.W.; Li, Z.; Francisco, G.; Lin, Y.I.; Petersen, P.J.; Yang, Y.; Kumagai, T.; Weiss, W.J.; Shlaes, D.M.; Knox, J.R.; Mansour, T.S. Structure-activity relationship of 6-methylidene penems bearing 6,5 bicyclic heterocycles as broad-spectrum β -lactamase inhibitors: Evidence for 1,4-thiazepine intermediates with C7 R stereochemistry by computational methods. J. Med. Chem., 2006, 49, 4623-4637.
40. 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., 2002, 2, 501-506.
41. Pacheco, O.J.A.; Bernardini, A.; Garcia-Leon, G.; Corona, F.; Sanchez, M.B.; Martinez, J.L. The intrinsic resistome of bacterial pathogens. Front. Microbiol., 2013, 4, 103.
42. Fleischmann, R.D.; Adams, M.D.; White, O.; Clayton, R.A.; Kirkness, E.F.; Kerlavage, A.R.; Bult, C.J.; Tomb, J.F.; Dougherty, B.A.; Merrick, J.M.; al, e. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science, 1995, 269, 496-512.
43. Goffeau, A.; Barrell, B.G.; Bussey, H.; Davis, R.W.; Dujon, B.; Feldmann, H.; Galibert, F.; Hoheisel, J.D.; Jacq, C.; Johnston, M.; Louis, E.J.; Mewes, H.W.; Murakami, Y.; Philippsen, P.; Tettelin, H.; Oliver, S.G. Life with 6000 genes. Science, 1996, 274, 546-567.
44. Blattner, F.R.; Plunkett, G., 3rd; Bloch, C.A.; Perna, N.T.; Burland, V.; Riley, M.; Collado-Vides, J.; Glasner, J.D.; Rode, C.K.; Mayhew, G.F.; Gregor, J.; Davis, N.W.; Kirkpatrick, H.A.; Goeden, M.A.; Rose, D.J.; Mau, B.; Shao, Y. The complete genome sequence of Escherichia coli K-12. Science, 1997, 277, 1453-1462.
45. National Center for Biotechnology Information (NCBI), genome information by organism, http://www.ncbi.nlm.nih.gov/genome/browse/
46. Chan, P.F.; Macarron, R.; Payne, D.J.; Zalacain, M.; Holmes, D.J. Novel antibacterials: a genomics approach to drug discovery. Curr. Drug Targets - Infect. Disord., 2002, 2, 291-308.
47. Marrakchi, H.; Dewolf, W.E.; Quinn, C.; West, J.; Polizzi, B.J.; So, C.Y.; Holmes, D.J.; Reed, S.L.; Heath, R.J.; Payne, D.J.; Rock, C.O.; Wallis, N.G. Characterization of Streptococcus pneumoniae enoyl-(acyl-carrier protein) reductase (FabK). Biochem. J., 2003, 370, 1055-1062.
48. Zhu, L.; Lin, J.; Ma, J.; Cronan, J.E.; Wang, H. Triclosan resistance of Pseudomonas aeruginosa PAO1 is due to FabV, a triclosan-resistant enoyl-acyl carrier protein reductase. Antimicrob. Agents Chemother., 2010, 54, 689-698.
49. Kaplan, N; Albert, M; Awrey, D; Bardouniotis, E; Berman, J; Clarke, T; Dorsey, M; Hafkin, B; Ramnauth, J; Romanov, V; Schmid, M.B.; Thalakada, R; Yethon, J; Pauls, H.W. Mode of action, in vitro activity, and in vivo efficacy of AFN-1252, a selective antistaphylococcal FabI inhibitor. Antimicrob. Agents Chemother., 2012, 56, 5865-5874.
50. Yao, J.; Maxwell, J.B.; Rock, C.O. Resistance to AFN-1252 arises from missense mutations in Staphylococcus aureus enoyl-acyl carrier protein reductase (FabI). J. Biol. Chem., 2013, 288, 36261-36271.
51. Karlowsky, J.A.; Kaplan, N.; Hafkin, B.; Hoban, D.J.; Zhanel, G.G. AFN-1252, a FabI inhibitor, demonstrates a Staphylococcus-specific spectrum of activity. Antimicrob. Agents Chemother., 2009, 53, 3544-3548.
52. Gallant, P.; Finn, J.; Keith, D.; Wendler, P. The identification of quality antibacterial drug discovery targets: a case study with aminoacyl-tRNA synthetases. Expert Opin. Ther. Targets, 2000, 4, 1-9.
53. Gentry, D.R.; Ingraham, K.A.; Stanhope, M.J.; Rittenhouse, S.; Jarvest, R.L.; O'Hanlon, P.J.; Brown, J.R.; Holmes, D.J. Variable sensitivity to bacterial methionyl-tRNA synthetase inhibitors reveals subpopulations of Streptococcus pneumoniae with two distinct methionyl-tRNA synthetase genes. Antimicrob. Agents Chemother., 2003, 47, 1784-1789.
54. Brinster, S.; Lamberet, G.; Staels, B.; Trieu-Cuot, P.; Gruss, A.; Poyart, C. Type II fatty acid synthesis is not a suitable antibiotic target for Gram-positive pathogens. Nature, 2009, 458, 83-86.
55. Wang, J.; Soisson, S.M.; Young, K.; Shoop, W.; Kodali, S.; Galgoci, A.; Painter, R.; Parthasarathy, G.; Tang, Y.S.; Cummings, R.; Ha, S.; Dorso, K.; Motyl, M.; Jayasuriya, H.; Ondeyka, J.; Herath, K.; Zhang, C.; Hernandez, L.; Allocco, J.; Basilio, Ã.n.; Tormo, J.R.; Genilloud, O.; Vicente, F.; Pelaez, F.; Colwell, L.; Lee, S.H.; Michael, B.; Felcetto, T.; Gill, C.; Silver, L.L.; Hermes, J.D.; Bartizal, K.; Barrett, J.; Schmatz, D.; Becker, J.W.; Cully, D.; Singh, S.B. Platensimycin is a selective FabF inhibitor with potent antibiotic properties. Nature, 2006, 441, 358-361.
56. Wang, J.; Kodali, S.; Lee, S.H.; Galgoci, A.; Painter, R.; Dorso, K.; Racine, F.; Motyl, M.; Hernandez, L.; Tinney, E.; Colletti, S.L.; Herath, K.; Cummings, R.; Salazar, O.; González, I.; Basilio, A.; Vicente, F.; Genilloud, O.; Pelaez, F.; Jayasuriya, H.; Young, K.; Cully, D.F.; Singh, S.B. Discovery of platencin, a dual FabF and FabH inhibitor with in vivo antibiotic properties. Proc. Nat. Acad. Sci., 2007, 104, 7612-7616.
57. Freiberg, C.; Brunner, N.A.; Schiffer, G.; Lampe, T.; Pohlmann, J.; Brands, M.; Raabe, M.; Häbich, D.; Ziegelbauer, K. Identification and characterization of the first class of potent bacterial acetyl-CoA carboxylase inhibitors with antibacterial activity. J. Biol. Chem., 2004, 279, 26066-26073.
58. von Nussbaum, F.; Brands, M.; Hinzen, B.; Weigand, S.; Häbich, D. Antibacterial natural products in medicinal chemistry-exodus or revival? Angew. Chem. Int. Ed., 2006, 45, 5072-5129.
59. Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev., 1997, 23, 3-25.
60. O'Shea, R.; Moser, H.E. Physicochemical properties of antibacterial compounds: implications for drug discovery. J. Med. Chem., 2008, 51, 2871-2878.
61. Wecke, T.; Mascher, T. Antibiotic research in the age of omics: from expression profiles to interspecies communication. J. Antimicrob. Chemother., 2011, 66, 2689-2704.
62. Lima, T.B.; Pinto, M.F.S.; Ribeiro, S.M.; de Lima, L.A.; Viana, J.C.; Júnior, N.G.; Cândido, E.d.S.; Dias, S.C.; Franco, O.L. Bacterial resistance mechanism: what proteomics can elucidate. FASEB J., 2013, 27, 1291-1303.
63. Romero, D.; Traxler, M.F.; López, D.; Kolter, R. Antibiotics as signal molecules. Chem. Rev., 2011, 111, 5492-5505.
64. Gauwerky, K.; Borelli, C.; Korting, H.C. Targeting virulence: A new paradigm for antifungals. Drug Discov. Today, 2009, 14, 214-222.
65. Alksne, L.E.; Projan, S.J. Bacterial virulence as a target for antimicrobial chemotherapy. Curr. Opin. Biotech., 2000, 11, 625-636.
66. Alekshun, M.N.; Levy, S.B. Targeting virulence to prevent infection: to kill or not to kill? Drug Discov. Today: Therap. Strategies, 2004, 1, 483-489.
67. Clatworthy, A.E.; Pierson, E.; Hung, D.T. Targeting virulence: a new paradigm for antimicrobial therapy. Nat. Chem. Biol., 2007, 3, 541-548.
68. Barczak, A.K.; Hung, D.T. Productive steps toward an antimicrobial targeting virulence. Curr. Opin. Microbiol., 2009, 12, 490-496.
69. Kandaswamy, K.; Liew, T.H.; Wang, C.Y.; Huston-Warren, E.; Meyer-Hoffert, U.; Hultenby, K.; Schröder, J.M.; Caparon, M.G.; Normark, S.; Henriques-Normark, B.; Hultgren, S.J.; Kline, K.A. Focal targeting by human β-defensin 2 disrupts localized virulence factor assembly sites in Enterococcus faecalis. Proc. Natl. Acad. Sci., 2013, 110, 20230-20235.
70. Rasmussen, T.B.; Bjarnsholt, T.; Skindersoe, M.E.; Hentzer, M.; Kristoffersen, P.; Köte, M.; Nielsen, J.; Eberl, L.; Givskov, M. Screening for quorum-sensing inhibitors (QSI) by use of a novel genetic system, the QSI selector. J. Bacteriol., 2005, 187, 1799-1814.
71. Lowy, I.; Molrine, D.C.; Leav, B.A.; Blair, B.M.; Baxter, R.; Gerding, D.N.; Nichol, G.; Thomas, W.D.; Leney, M.; Sloan, S.; Hay, C.A.; Ambrosino, D.M. Treatment with monoclonal antibodies against Clostridium difficile toxins. N. Engl. J. Med., 2010, 362, 197-205.
72. López, E.L.; Contrini, M.M.; Glatstein, E.; González Ayala, S.; Santoro, R.; Allende, D.; Ezcurra, G.; Teplitz, E.; Koyama, T.; Matsumoto, Y.; Sato, H.; Sakai, K.; Hoshide, S.; Komoriya, K.; Morita, T.; Harning, R.; Brookman, S. Safety and pharmacokinetics of urtoxazumab, a humanized monoclonal antibody, against Shiga-like toxin 2 in healthy adults and in pediatric patients infected with Shiga-like toxin-producing Escherichia coli. Antimicrob. Agents Chemother., 2010, 54, 239-243.
73. Allen, R.C.; Popat, R.; Diggle, S.P.; Brown, S.P. Targeting virulence: can we make evolution-proof drugs? Nat. Rev. Microbiol., 2014, 12, 300-308.
74. Gordon, C.P.; Williams, P.; Chan, W.C. Attenuating Staphylococcus aureus virulence gene regulation: A medicinal chemistry perspective. J. Med. Chem., 2013, 56, 1389-1404.
75. Rampioni, G.; Leoni, L.; Williams, P. The art of antibacterial warfare: Deception through interference with quorum sensing-mediated communication. Bioorg. Chem., 2014, 55, 60-68.
76. Antunes, L.C.M.; Ferreira, R.B.R.; Buckner, M.M.C.; Finlay, B.B. Quorum sensing in bacterial virulence. Microbiol., 2010, 156, 2271-2282.
77. Keller, L.; Surette, M.G. Communication in bacteria: an ecological and evolutionary perspective. Nat. Rev. Microbiol., 2006, 4, 249-258.
78. Geske, G.D.; O'Neill, J.C.; Blackwell, H.E. Expanding dialogues: from natural autoinducers to non-natural analogues that modulate quorum sensing in Gram-negative bacteria. Chem. Soc. Rev., 2008, 37, 1432-1447.
79. Zhu, J.; Kaufmann, G.F. Quo vadis quorum quenching? Curr. Opin. Pharmacol., 2013, 13, 688-698.
80. Miller, M.B.; Bassler, B.L. Quorum sensing in bacteria. Annu. Rev. Microbiol., 2001, 55, 165-199.
81. Pappas, K.M.; Weingart, C.L.; Winans, S.C. Chemical communication in proteobacteria: biochemical and structural studies of signal synthases and receptors required for intercellular signalling. Mol. Microbiol., 2004, 53, 755-769.
82. Gould, T.A.; Watson, W.T.; Choi, K.H.; Schweizer, H.P.; Churchill, M.E.A. Crystallization of Pseudomonas aeruginosa AHL synthase LasI using β-turn crystal engineering. Acta Crystallogr. Sect. D: Biol. Crystallogr., 2004, 60, 518-520.
83. Parsek, M.R.; Val, D.L.; Hanzelka, B.L.; Cronan, J.E.; Greenberg, E.P. Acyl homoserine-lactone quorum-sensing signal generation. Proc. Natl. Acad. Sci., 1999, 96, 4360-4365.
84. Chung, J.; Goo, E.; Yu, S.; Choi, O.; Lee, J.; Kim, J.; Kim, H.; Igarashi, J.; Suga, H.; Moon, J.S.; Hwang, I.; Rhee, S. Small-molecule inhibitor binding to an N-acyl-homoserine lactone synthase. Proc. Natl. Acad. Sci., 2011, 108, 12089-12094.
85. Rasmussen, T.B.; Givskov, M. Quorum-sensing inhibitors as antipathogenic drugs. Int. J. Med. Microbiol., 2006, 296, 149-161.
86. Eberhard, A.; Widrig, C.; McBath, P.; Schineller, J. Analogs of the autoinducer of bioluminescence in Vibrio fischeri. Arch. Microbiol., 1986, 146, 35-40.
87. Schaefer, A.L.; Hanzelka, B.L.; Eberhard, A.; Greenberg, E.P. Quorum sensing in Vibrio fischeri: probing autoinducer-LuxR interactions with autoinducer analogs. J. Bacteriol., 1996, 178, 2897-2901.
88. Janssens, J.C.A.; Metzger, K.; Daniels, R.; Ptacek, D.; Verhoeven, T.; Habel, L.W.; Vanderleyden, J.; De Vos, D.E.; De Keersmaecker, S.C.J. Synthesis of N-acyl homoserine lactone analogues reveals strong activators of Sdia, the Salmonella enterica Serovar typhimurium luxr homologue. Appl. Environ. Microbiol., 2007, 73, 535-544.
89. Reverchon, S.; Chantegrel, B.; Deshayes, C.; Doutheau, A.; Cotte-Pattat, N. New synthetic analogues of N-acyl homoserine lactones as agonists or antagonists of transcriptional regulators involved in bacterial quorum sensing. Bioorg. Med. Chem. Lett., 2002, 12, 1153-1157.
90. Castang, S.; Chantegrel, B.; Deshayes, C.; Dolmazon, R.; Gouet, P.; Haser, R.; Reverchon, S.; Nasser, W.; Hugouvieux-Cotte-Pattat, N.; Doutheau, A. N-Sulfonyl homoserine lactones as antagonists of bacterial quorum sensing. Bioorg. Med. Chem. Lett., 2004, 14, 5145-5149.
91. Frezza, M.; Castang, S.; Estephane, J.; Soulere, L.; Deshayes, C.; Chantegrel, B.; Nasser, W.; Queneau, Y.; Reverchon, S.; Doutheau, A. Synthesis and biological evaluation of homoserine lactone derived ureas as antagonists of bacterial quorum sensing. Bioorg. Med. Chem., 2006, 14, 4781-4791.
92. Li, M.; Ni, N.; Chou, H.T.; Lu, C.D.; Tai, P.C.; Wang, B. Structure-based discovery and experimental verification of novel AI-2 quorum sensing inhibitors against Vibrio harveyi. ChemMedChem, 2008, 3, 1242-1249.
93. Peng, H.; Cheng, Y.; Ni, N.; Li, M.; Choudhary, G.; Chou, H.T.; Lu, C.D.; Tai, P.C.; Wang, B. Synthesis and evaluation of new antagonists of bacterial quorum sensing in Vibrio harveyi. ChemMedChem, 2009, 4, 1457-1468.
94. Zhu, P.; Peng, H.; Ni, N.; Wang, B.; Li, M. Novel AI-2 quorum sensing inhibitors in Vibrio harveyi identified through structure-based virtual screening. Bioorg. Med. Chem. Lett., 2012, 22, 6413-6417.
95. Schuster, M.; Joseph Sexton, D.; Diggle, S.P.; Peter Greenberg, E. Acyl-homoserine lactone quorum sensing: From evolution to application. Annu. Rev. Microbiol., 2013, 67, 43-63.
96. Dionne, M.S.; Ghori, N.; Schneider, D.S. Drosophila melanogaster is a genetically tractable model host for Mycobacterium marinum. Infect. Immun., 2003, 71, 3540-3550.
97. Jander, G.; Rahme, L.G.; Ausubel, F.M. Positive correlation between virulence of Pseudomonas aeruginosa mutants in mice and insects. J. Bacteriol., 2000, 182, 3843-3845.
98. D'Argenio, D.A.; Gallagher, L.A.; Berg, C.A.; Manoil, C. Drosophila as a model host for Pseudomonas aeruginosa infection. J. Bacteriol., 2001, 183, 1466-1471.
99. Fuqua, C.; Greenberg, E.P. Listening in on bacteria: acylhomoserine lactone signalling. Nat. Rev. Mol. Cell Biol., 2002, 3, 685-695.
100. Marra, A. Can virulence factors be viable antibacterial targets? Expert Rev. Anti-infect. Ther., 2004, 2, 61-72.
101. Bjarnsholt, T.; Givskov, M. Quorum-sensing blockade as a strategy for enhancing host defences against bacterial pathogens. Philos. Trans. R. Soc. B: Biol. Sci., 2007, 362, 1213-1222.
102. Waters, C.M.; Bassler, B.L. Quorum sensing: cell-to-cell communication in bacteria. Annu. Rev. Cell Dev. Biol., 2005, 21, 319-346.
103. Wadhams, G.H.; Armitage, J.P. Making sense of it all: bacterial chemotaxis. Nat. Rev. Mol. Cell Biol., 2004, 5, 1024-1037.
104. Stephenson, K.; Hoch, J.A. Virulence- and antibiotic resistance-associated two-component signal transduction systems of Gram-positive pathogenic bacteria as targets for antimicrobial therapy. Pharmacol. Ther., 2002, 93, 293-305.
105. Parkinson, J.S.; Kofoid, E.C. Communication modules in bacterial signaling proteins. Annu. Rev. Genet., 1992, 26, 71-112.
106. Hoch, J.A.; Varughese, K.I. Keeping signals straight in phosphorelay signal transduction. J. Bacteriol., 2001, 183, 4941-4949.
107. Barrett, J.F.; Goldschmidt, R.M.; Lawrence, L.E.; Foleno, B.; Chen, R.; Demers, J.P.; Johnson, S.; Kanojia, R.; Fernandez, J.; Bernstein, J.; Licata, L.; Donetz, A.; Huang, S.; Hlasta, D.J.; Macielag, M.J.; Ohemeng, K.; Frechette, R.; Frosco, M.B.; Klaubert, D.H.; Whiteley, J.M.; Wang, L.; Hoch, J.A. Antibacterial agents that inhibit two-component signal transduction systems. Proc. Natl. Acad Sci., 1998, 95, 5317-5322.
108. Roychoudhury, S.; Collins, S.M.; Hynd, B.A.; Parker, C.N. High throughput autophosphorylation assay for bacterial protein histidine kinases. J. Biomol. Screen., 1997, 2, 85-90.
109. Moellering, R.C. Antibiotic resistance: lessons for the future. Clin. Infect. Dis., 1998, 27, S135-S140.
110. Zhang, Y.; Mitchison, D. The curious characteristics of pyrazinamide: a review. Int. J. Tuberc. Lung Dis., 2003, 7, 6-21.
111. Hu, Y.; Coates, A.R.; Mitchison, D.A. Sterilising action of pyrazinamide in models of dormant and rifampicin-tolerant Mycobacterium tuberculosis. Int. J. Tuberc. Lung Dis., 2006, 10, 317-322.
112. Hu, Y.; Coates, A.R.M.; Mitchison, D.A. Sterilizing activities of fluoroquinolones against rifampin-tolerant populations of Mycobacterium tuberculosis. Antimicrob. Agents Chemother., 2003, 47, 653-657.
113. Singh, R.; Manjunatha, U.; Boshoff, H.I.M.; Ha, Y.H.; Niyomrattanakit, P.; Ledwidge, R.; Dowd, C.S.; Lee, I.Y.; Kim, P.; Zhang, L.; Kang, S.; Keller, T.H.; Jiricek, J.; Barry, C.E. PA-824 kills nonreplicating Mycobacterium tuberculosis by intracellular NO release. Science, 2008, 322, 1392-1395.
114. Ji, B.; Chauffour, A.; Andries, K.; Jarlier, V. Bactericidal activities of R207910 and other newer antimicrobial agents against Mycobacterium leprae in mice. Antimicrob. Agents Chemother., 2006, 50, 1558-1560.
115. Matsumoto, M.; Hashizume, H.; Tomishige, T.; Kawasaki, M.; Tsubouchi, H.; Sasaki, H.; Shimokawa, Y.; Komatsu, M. OPC-67683, a nitro-dihydro-imidazooxazole derivative with promising action against Tuberculosis in vitro and in mice. PLoS Med, 2006, 3, e466.
116. Protopopova, M.; Hanrahan, C.; Nikonenko, B.; Samala, R.; Chen, P.; Gearhart, J.; Einck, L.; Nacy, C.A. Identification of a new antitubercular drug candidate, SQ109, from a combinatorial library of 1,2-ethylenediamines. J. Antimicrob. Chemother., 2005, 56, 968-974.
117. LL-3858. Tuberculosis (Edinburgh, Scotl.), 2008, 88 (2), 126.
118. Manjunatha, U.; Boshoff, H.I.; Barry, C.E. The mechanism of action of PA-824: Novel insights from transcriptional profiling. Commun. Integr. Biol., 2009, 2, 215-218.
119. Ooi, N.; Miller, K.; Randall, C.; Rhys-Williams, W.; Love, W.; Chopra, I. XF-70 and XF-73, novel antibacterial agents active against slow-growing and non-dividing cultures of Staphylococcus aureus including biofilms. J. Antimicrob. Chemother., 2010, 65, (1), 72-78.
120. Hu, Y.; Shamaei-Tousi, A.; Liu, Y.; Coates, A. A new approach for the discovery of antibiotics by targeting non-multiplying bacteria: A novel topical antibiotic for Staphylococcal infections. PLoS ONE, 2010, 5, e11818.
121. Hu, Y.; Coates, A.R.M. Enhancement by novel anti-methicillin-resistant Staphylococcus aureus compound HT61 of the activity of neomycin, gentamicin, mupirocin and chlorhexidine: in vitro and in vivo studies. J. Antimicrob. Chemother., 2012, 68(2), 374-384.
122. Cherian, P.T.; Wu, X.; Maddox, M.M.; Singh, A.P.; Lee, R.E.; Hurdle, J.G. Chemical modulation of the biological activity of reutericyclin: a membrane-active antibiotic from Lactobacillus reuteri. Sci. Rep., 2014, 4, 4721.
123. Rami, A.; Toutain, C.M.; Jacq, A. An increased level of alternative sigma factor RpoS partially suppresses drug hypersensitivity associated with inactivation of the multidrug resistance pump AcrAB in Escherichia coli. Res. Microbiol., 2005, 156, 356-360.
124. Murakami, K.; Ono, T.; Viducic, D.; Kayama, S.; Mori, M.; Hirota, K.; Nemoto, K.; Miyake, Y. Role for rpoS gene of Pseudomonas aeruginosa in antibiotic tolerance. FEMS Microbiol. Lett., 2005, 242, 161-167.
125. Pepper, E.D.; Farrell, M.J.; Finkel, S.E. Role of penicillin-binding protein 1b in competitive stationary-phase survival of Escherichia coli. FEMS Microbiol. Lett., 2006, 263, 61-67.
126. Hu, Y.; Coates, A.R.M. Transposon mutagenesis identifies genes which control antimicrobial drug tolerance in stationary-phase Escherichia coli. FEMS Microbiol. Lett., 2005, 243, 117-124.
127. Coates, A.R.M.; Hu, Y. Targeting non-multiplying organisms as a way to develop novel antimicrobials. Trends Pharmacol. Sci., 2008, 29, 143-150.
128. Jefferson, K.K.; Goldmann, D.A.; Pier, G.B. Use of confocal microscopy to analyze the rate of vancomycin penetration through Staphylococcus aureus biofilms. Antimicrob. Agents Chemother., 2005, 49, 2467-2473.
129. Zhang, Y. Persisters, persistent infections and the Yin-Yang model. Emerg. Microbes Infect., 2014, 3, e3.
130. Lewis, K. Persister cells, dormancy and infectious disease. Nat. Rev. Microbiol., 2007, 5, 48-56.
131. Mitchison, D.A. Antimicrobial therapy of tuberculosis: justification for currently recommended treatment regimens. Semin. Respir. Crit. Care Med., 2004, 25, 307-315.
132. MacGowan, A.; Bowker, K. Developments in PK/PD: optimising efficacy and prevention of resistance. A critical review of PK/PD in in vitro models. Int. J. Antimicrob. Agents, 2002, 19, 291-298.
133. Pan, J.; Bahar, A.A.; Syed, H.; Ren, D. Reverting antibiotic tolerance of Pseudomonas aeruginosa PAO1 persister cells by Z-4-bromo-5-(bromomethylene)-3-methylfuran-2(5H)-one. PLoS ONE, 2012, 7, e45778.
134. Pan, J.; Xie, X.; Tian, W.; Bahar, A.; Lin, N.; Song, F.; An, J.; Ren, D. (Z)-4-Bromo-5-(bromomethylene)-3-methylfuran-2(5H)-one sensitizes Escherichia coli persister cells to antibiotics. Appl. Microbiol. Biotechnol., 2013, 97, 9145-9154.
135. Duckworth, D.H. "Who discovered bacteriophage?". Bacteriol. Rev., 1976, 40, 793-802.
136. Skurnik, M.; Strauch, E. Phage therapy: facts and fiction. Int. J. Med. Microbiol., 2006, 296, 5-14.
137. Borysowski, J.; Weber-Dabrowska, B.; Gorski, A. Bacteriophage endolysins as a novel class of antibacterial agents. Exp. Biol. Med., 2006, 231, 366-377.
138. Abedon, S.T.; Kuhl, S.J.; Blasdel, B.G.; Kutter, E.M. Phage treatment of human infections. Bacteriophage, 2011, 1, 66-85.
139. Gill, J.J.; Hyman, P. Phage choice, isolation, and preparation for phage therapy. Curr. Pharm. Biotech., 2010, 11, 2-14.
140. Jagusztyn-Krynicka Ek Fau - Wyszynska, A.; Wyszynska, A. The decline of antibiotic era-new approaches for antibacterial drug discovery. Pol. J. Microbiol., 2008, 57, 91-98.
141. Rogers, G.B.; Carroll, M.P.; Bruce, K.D. Enhancing the utility of existing antibiotics by targeting bacterial behaviour? Br. J. Pharmacol., 2012, 165, 845-857.
142. Kutateladze, M.; Adamia, R. Bacteriophages as potential new therapeutics to replace or supplement antibiotics. Trends Biotech., 2010, 28, 591-595.
143. Abdul-Hassan, H.; El-Tahan, E.; Massoud, B.; Gomaa, R. Bacteriophage therapy of Pseudomonas burn wound sepsis. Ann. Medit. Burn Club, 1990, 3, 262-264.
144. Jikia, D.; Chkhaidze, N.; Imedashvili, E.; Mgaloblishvili, I.; Tsitlanadze, G.; Katsarava, R.; Glenn Morris, J.; Sulakvelidze, A. The use of a novel biodegradable preparation capable of the sustained release of bacteriophages and ciprofloxacin, in the complex treatment of multidrug-resistant Staphylococcus aureus-infected local radiation injuries caused by exposure to Sr90. Clin. Exp. Dermat., 2005, 30, 23-26.
145. Lazareva, E.B.; Smirnov, S.V.; Khvatov, V.B.; Spiridonova, T.G.; Bitkova, E.E.; Darbeeva, O.S.; Maiskaia, L.M.; Parfeniuk, R.L.; Men'shikov, D.D. Efficacy of bacteriophages in complex treatment of patients with burn wounds. Antibiot. Khimioter., 2001, 46, 10-14.
146. McVay, C.S.; Velásquez, M.; Fralick, J.A. Phage therapy of Pseudomonas aeruginosa infection in a mouse burn wound model. Antimicrob. Agents Chemother., 2007, 51, 1934-1938.
147. Paul, V.D.; Sundarrajan, S.; Rajagopalan, S.S.; Hariharan, S.; Kempashanaiah, N.; Padmanabhan, S.; Sriram, B.; Ramachandran, J. Lysis-deficient phages as novel therapeutic agents for controlling bacterial infection. BMC Microbiol., 2011, 11, 195.
148. Abedon, S.T. Phage therapy: Eco-physiological pharmacology. Scientifica, 2014, Article ID 581639, 29 pages, http://dx.doi.org/10.1155/2014/581639
149. Kutter, E.; De Vos, D.; Gvasalia, G.; Alavidze, Z.; Gogokhia, L.; Kuhl, S.; Abedon, S.T. Phage therapy in clinical practice: Treatment of human infections. Curr. Pharm. Biotechnol., 2010, 11, 69-86.
150. Verbeken, G.; Pirnay, J.P.; Lavigne, R.; Jennes, S.; De Vos, D.; Casteels, M.; Huys, I. Call for a dedicated European legal framework for bacteriophage therapy. Arch. Immunol. Ther. Exp. (Warsz), 2014, 62, 117-129.
151. Huys, I.; Pirnay, J.P.; Lavigne, R.; Jennes, S.; De Vos, D.; Casteels, M.; Verbeken, G. Paving a regulatory pathway for phage therapy. EMBO Reports, 2013, 14, 951-954.