Antibiotic discovery: Where have we come from, where do we go?

Antibiotics

Volumn 8, Issue 2, 2019, Pages

  da Cunha, Bernardo Ribeiro ^a   Fonseca, Luís P ^a   Calado, Cecília R C ^b  

^a INSTITUTO SUPERIOR TÉCNICO   (Portugal)

^b INSTITUTO SUPERIOR DE ENGENHARIA DE LISBOA   (Portugal)

Author keywords

Antibiotic discovery platforms; Drug screening; Fully synthetic antibiotics; Genomics; Lipidomics; Metabolomics; Metagenomics; Proteomics; Semi synthesis

Indexed keywords

2,4 DIAMINOPYRIMIDINE DERIVATIVE; AMINOGLYCOSIDE; ANSAMYCIN DERIVATIVE; ANTIBIOTIC AGENT; BETA LACTAM ANTIBIOTIC; CHLORAMPHENICOL; FOSFOMYCIN; GLYCOPEPTIDE; IMIDAZOLE; LIPOPEPTIDE; MACROLIDE; OXAZOLIDINONE DERIVATIVE; POLYMYXIN; QUINOLONE DERIVATIVE; STREPTOGRAMIN DERIVATIVE; SULFONAMIDE; TETRACYCLINE;

ACTINOBACTERIA; AMYCOLATOPSIS MEDITERRANEI; ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; ANTIMICROBIAL ACTIVITY; BACILLUS SUBTILIS; BACTERIAL GENOME; BACTERIAL GROWTH; BIOINFORMATICS; CANCER RESISTANCE; DRUG DEVELOPMENT; ESCHERICHIA COLI; GENE EXPRESSION; GENETIC TRANSCRIPTION; GENETIC VARIABILITY; GENOMICS; HIGH THROUGHPUT SCREENING; LIPID ANALYSIS; LIPIDOMICS; METABOLOMICS; METAGENOMICS; MICROBIAL METABOLISM; MULTIDRUG RESISTANCE; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN SYNTHESIS; PROTEOMICS; REVIEW; SIGNAL TRANSDUCTION; STAPHYLOCOCCUS AUREUS; STREPTOCOCCUS PNEUMONIAE; STREPTOMYCES GRISEUS; TRANSCRIPTOMICS; TUMOR MICROENVIRONMENT;

EID: 85067059407     PISSN: None     EISSN: 20796382     Source Type: Journal    
DOI: 10.3390/antibiotics8020045     Document Type: Review

References (145)

1. Smith, P.W.; Watkins, K.; Hewlett, A. Infection control through the ages. Am. J. Infect. Control 2012, 40, 35–42.
2. Clardy, J.; Fischbach, M.A.; Currie, C.R. The natural history of antibiotics. Curr. Biol. 2009, 19, 437–441.
3. Livermore, D.M. Discovery research: The scientific challenge of finding new antibiotics. J. Antimicrob. Chemother. 2011, 66, 1941–1944.
4. Saga, T.; Yamaguchi, K. History of antimicrobial agents and resistant. Jpn. Med. Assoc. J. 2009, 137, 103–108.
5. WHO Report on Global Surveillance of Epidemic-prone Infectious Diseases—Introduction Available online: Http://www.who.int/csr/resources/publications/introduction/en/index1.html (accessed on 12 October 2018).
6. Center for Disease Control and Prevention. Antibiotic Use in the United States, 2017: Progress and Opportunities; US Department of Health and Human Service: Atlanta, GA, USA, 2017; pp. 1–40.
7. Cassini, A.; Högberg, L.D.; Plachouras, D.; Quattrocchi, A.; Hoxha, A.; Simonsen, G.S.; Colomb-Cotinat, M.; Kretzschmar, M.E.; Devleesschauwer, B.; Cecchini, M., et al. Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: A population-level modelling analysis. Lancet Infect. Dis. 2018, 3099, 1–11.
8. European Centre for Disease Prevention and Control; European Medicines Agency The Bacterial Challenge: Time to React; European Centre for Disease Prevention and Control: Stockholm, Sweden, 2009; Volume 6. ISBN 9789291931934.
9. Laxminarayan, R.; Matsoso, P.; Pant, S.; Brower, C.; Røttingen, J.A.; Klugman, K.; Davies, S. Access to effective antimicrobials: A worldwide challenge. Lancet 2016, 387, 168–175.
10. Martens, E.; Demain, A.L. The antibiotic resistance crisis, with a focus on the United States. J. Antibiot. 2017, 70, 520–526.
11. Akova, M. Epidemiology of antimicrobial resistance in bloodstream infections. Virulence 2016, 7, 252–266.
12. McFee, R.B. Nosocomial or hospital-acquired infections: An overview. Dis. Mon. 2009, 55, 422–438.
13. Theuretzbacher, U. Accelerating resistance, inadequate antibacterial drug pipelines and international responses. Int. J. Antimicrob. Agents 2012, 39, 295–299.
14. Frieri, M.; Kumar, K.; Boutin, A. Antibiotic resistance. J. Infect. Public Heal. 2017, 10, 369–378, doi:10.1016/j.jiph.2016.08.007.
15. Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations. Available online: Https://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations_1.pdf (accessed on 24 March 2019).
16. Rather, I.A.; Kim, B.C.; Bajpai, V.K.; Park, Y.H. Self-medication and antibiotic resistance: Crisis, current challenges, and prevention. Saudi J. Biol. Sci. 2017, 24, 808–812.
17. Dodds, D.R. Antibiotic resistance: A current epilogue. Biochem. Pharmacol. 2017, 134, 139–146.
18. Renwick, M.J.; Brogan, D.M.; Mossialos, E. A systematic review and critical assessment of incentive strategies for discovery and development of novel antibiotics. J. Antibiot. 2016, 69, 73–88.
19. Smith, D. Antibiotics Are Money-Losers For Big Pharma. How Can We Incentivize the Development of New Ones? Available online: Https://www.forbes.com/sites/quora/2018/01/02/antibiotics-are-money-losers-for-big-pharma-how-can-we-incentivize-the-development-of-new-ones/#9318630487f3 (accessed on 23 March 2019).
20. Kostyanev, T.; Bonten, M.J.M.; Steel, H.; Ross, S.; Franc, B.; Tacconelli, E.; Winterhalter, M.; Stavenger, R.A.; Harbarth, S.; Hackett, J., et al. The innovative medicines initiative’s new drugs for bad bugs programme: European public—Private partnerships for the development of new strategies to tackle antibiotic resistance. J. Antimicrob. Chemother. 2016, 71, 290–295.
21. Boucher, H.W.; Talbot, G.H.; Bradley, J.S.; Edwards, J.E.; Gilbert, D.; Rice, L.B.; Scheld, M.; Spellberg, B.; Bartlett, J. Bad bugs, no drugs: No ESKAPE! An update from the infectious diseases society of America. Clin. Infect. Dis. 2009, 48, 1–12.
22. Brown, D.G. New drugs and emerging leads in antibacterial drug discovery. Ref. Modul. Chem. Mol. Sci. Chem. Eng. 2016, doi:10.1016/B978-0-12-409547-2.12409-6.
23. The Pew Charitable Trusts Antibiotics Currently in Global Clinical Development Available online: Https://www.pewtrusts.org/en/research-and-analysis/data-visualizations/2014/antibiotics-currently-in-clinical-development (accessed on 23 March 2019).
24. Lewis, K. Platforms for antibiotic discovery. Nat. Rev. Drug Discov. 2013, 12, 371–387.
25. Tommasi, R.; Brown, D.G.; Walkup, G.K.; Manchester, J.I.; Miller, A.A. ESKAPEing the labyrinth of antibacterial discovery. Nat. Rev. Drug Discov. 2015, 14, 529–542.
26. Czaplewski, L.; Bax, R.; Clokie, M.; Dawson, M.; Fairhead, H.; Fischetti, V.A.; Foster, S.; Gilmore, B.F.; Hancock, R.E.W.; Harper, D., et al. Alternatives to antibiotics-a pipeline portfolio review. Lancet Infect. Dis. 2016, 16, 239–251.
27. Herrmann, M.; Nkuiya, B.; Dussault, A.R. Innovation and antibiotic use within antibiotic classes: Market incentives and economic instruments. Resour. Energy Econ. 2013, 35, 582–598.
28. Aminov, R.I. A brief history of the antibiotic era: Lessons learned and challenges for the future. Front. Microbiol. 2010, 1, 134.
29. Cui, L.; Su, X. Discovery, mechanisms of action and combination therapy of artemisinin. Expert Rev. Anti. Infect. Ther. 2009, 7, 999–1013.
30. Fetzner, S.; Drees, S.L. Old molecules, new biochemistry. Chem. Biol. 2013, 20, 1438–1440.
31. Nicholson, D.J. Biological atomism and cell theory. Stud. Hist. Philos. Sci. Part C Stud. Hist. Philos. Biol. Biomed. Sci. 2010, 41, 202–211.
32. Levine, R.; Evers, C. The Slow Death of Spontaneous Generation; North Carolina State University: Raleigh, NC, USA, 2000; pp. 7–8.
33. Brack, A. The Molecular Origins of Life: Assembling Pieces of the Puzzle. Cambridge University Press: Cambridge UK. 1998.
34. Newsom, S.W.B. Pioneers in infection control—Joseph Lister. J. Hosp. Infect. 2003, 55, 246–253.
35. Strebhardt, K.; Ullrich, A. Paul Ehrlich’s magic bullet concept: 100 Years of progress. Nat. Rev. Cancer 2008, 8, 473–480.
36. Williams, K.J. The introduction of “chemotherapy” using arsphenamine—The first magic bullet. J. R. Soc. Med. 2009, 102, 343–348.
37. Ferrie, J.E. Arsenic, antibiotics and interventions. Int. J. Epidemiol. 2014, 43, 977–982.
38. Wainwright, M.; Kristiansen, J.E. On the 75th anniversary of Prontosil. Dyes Pigments 2011, 88, 231–234.
39. Ligon, B.L. Penicillin: Its discovery and early development. Semin. Pediatr. Infect. Dis. 2004, 15, 52–57.
40. Fleming, A. Sir Alexander Fleming—Nobel Lecture Available online: Https://www.nobelprize.org/prizes/medicine/1945/fleming/lecture/ (accessed on 12 November 2018).
41. Bynum, B. Rediscovering penicillin. Lancet 2018, 392, 1108–1109.
42. Sales, K.C.; Rosa, F.; Sampaio, P.N.; Fonseca, L.P.; Lopes, M.B.; Calado, C.R.C. In situ near-infrared (NIR) versus high-throughput mid-infrared (MIR) spectroscopy to monitor biopharmaceutical production. Appl. Spectrosc. 2015, 69, 760–772.
43. Bentley, R. Different roads to discovery; Prontosil (hence sulfa drugs) and penicillin (hence β-lactams). J. Ind. Microbiol. Biotechnol. 2009, 36, 775–786.
44. Woodruff, H.B.; Selman, A. Waksman, winner of the 1952 nobel prize for physiology or medicine. Appl. Environ. Microbiol. 2014, 80, 2–8.
45. Lewis, K. Recover the lost art of drug discovery. Nature 2012, 485, 439–440.
46. Willey, J.; Sherwood, L.; Woolverton, C. Antimicrobial chemotherapy. In Prescott, Harley and Klein’s Microbiology; Willey, J., Sherwood, L., Woolverton, C., Eds.; Colin Wheatley/Janice Roerig-Blong: New York, NY, USA, 2008; pp. 835–837. ISBN 978–0–07–299291–5.
47. Wainwright, M. Streptomycin: Discovery and resultant controversy. Hist. Philos. Life Sci. 1991, 13, 97–124.
48. Wiest, D.B.; Cochran, J.B.; Tecklenburg, F.W. Chloramphenicol toxicity revisited: A 12-year-old patient with a brain abscess. J. Pediatr. Pharmacol. Ther. 2012, 17, 182–188.
49. Liu, F.; Myers, A.G. Development of a platform for the discovery and practical synthesis of new tetracycline antibiotics. Curr. Opin. Chem. Biol. 2016, 32, 48–57.
50. Cyphert, E.; Wallat, J.; Pokorski, J.; von Recum, H. Erythromycin modification that improves its acidic stability while optimizing it for local drug delivery. Antibiotics 2017, 6, 11.
51. Mast, Y.; Wohlleben, W. Streptogramins—Two are better than one! Int. J. Med. Microbiol. 2014, 304, 44–50.
52. James, R.C.; Pierce, J.G.; Okano, A.; Xie, J.; Boger, D.L. Redesign of glycopeptide antibiotics: Back to the future. ACS Chem. Biol. 2012, 7, 797–804.
53. Floss, H.G.; Yu, T. Rifamycin mode of action, resistance, and biosynthesis. Chem. Rev. 2005, 105, 621–632.
54. Michalopoulos, A.S.; Livaditis, I.G.; Gougoutas, V. The revival of fosfomycin. Int. J. Infect. Dis. 2011, 15, e732–e739.
55. Levin, A.S.; Barone, A.A.; Penço, J.; Santos, M.V.; Marinho, I.S.; Arruda, E.A.G.; Manrique, E.I.; Costa, S.F. Intravenous colistin as therapy for nosocomial infections caused by multidrug‐resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Clin. Infect. Dis. 1999, 28, 1008–1011.
56. Eisenstein, B.I.; Oleson, Jr., F.B.; Baltz, R.H. Daptomycin: From the mountain to the clinic, with essential help from Francis Tally, MD. Clin. Infect. Dis. 2010, 50, S10–S15.
57. Taylor, S.D.; Palmer, M. The action mechanism of daptomycin. Bioorg. Med. Chem. 2016, 24, 6253–6268.
58. Adeyemo, A.A.; Oluwatosin, O.; Omotade, O.O. Study of streptomycin-induced ototoxicity: Protocol for a longitudinal study. Springerplus 2016, 5, 758.
59. Townsend, C.A. Convergent biosynthetic pathways to β-lactam antibiotics. Curr. Opin. Chem. Biol. 2016, 35, 97–108.
60. Güngör, Ö.Ö.N.; Gürkan, P.; Özçelik, B.; Oyardi, Ö. Synthesis and antimicrobial activities of new higher amino acid Schiff base derivatives of 6-aminopenicillanic acid and 7-aminocephalosporanic acid. J. Mol. Struct. 2016, 1106, 181–191.
61. Deng, S.; Ma, X.; Su, E.; Wei, D. Efficient cascade synthesis of ampicillin from penicillin G potassium salt using wild and mutant penicillin G acylase from Alcaligenes faecalis. J. Biotechnol. 2016, 219, 142–148.
62. Gröger, H.; Pieper, M.; König, B.; Bayer, T.; Schleich, H. Industrial landmarks in the development of sustainable production processes for the β-lactam antibiotic key intermediate 7-aminocephalosporanic acid (7-ACA). Sustain. Chem. Pharm. 2017, 5, 72–79.
63. Hu, Y.; Zhu, B. Study on genetic engineering of Acremonium chrysogenum, the cephalosporin C producer. Synth. Syst. Biotechnol. 2016, 1, 143–149.
64. Nelson, M.L.; Levy, S.B. The history of the tetracyclines. Ann. N. Y. Acad. Sci. 2011, 1241, 17–32.
65. Charest, M.G.; Lerner, C.D.; Brubaker, J.D.; Siegel, D.R.; Myers, A.G. A convergent enantioselective route to structurally diverse 6-deoxytetracycline antibiotics. Science 2005, 308, 395–398.
66. Perez, M.; Echeverria, P.G.; Martinez-Arripe, E.; Ez Zoubir, M.; Touati, R.; Zhang, Z.; Genet, J.P.; Phansavath, P.; Ayad, T.; Ratovelomanana-Vidal, V. An efficient stereoselective total synthesis of all stereoisomers of the antibiotic thiamphenicol through ruthenium-catalyzed asymmetric reduction by dynamic kinetic resolution. Eur. J. Org. Chem. 2015, 2015, 5949–5958.
67. Alauzet, C.; Lozniewski, A.; Marchandin, H. Metronidazole resistance and nim genes in anaerobes: A review. Anaerobe 2019, 55, 40–53.
68. Wright, P.M.; Seiple, I.B.; Myers, A.G. The evolving role of chemical synthesis in antibacterial drug discovery. Angew. Chem.—Int. Ed. 2014, 53, 8840–8869.
69. Caron, F.; Wehrle, V.; Etienne, M. Triméthoprime: Un antibiotique en voie de réhabilitation en France. Med. Mal. Infect. 2017, 47, 253–260.
70. Bisacchi, G.S. Origins of the quinolone class of antibacterials: An expanded “discovery story.” J. Med. Chem. 2015, 58, 4874–4882.
71. Lee, G.C.; Reveles, K.R.; Attridge, R.T.; Lawson, K.A.; Mansi, I.A.; Lewis, J.S.; Frei, C.R. Outpatient antibiotic prescribing in the United States: 2000 to 2010. BMC Med. 2014, 12, 96.
72. Seiple, I.B.; Zhang, Z.; Jakubec, P.; Langlois-Mercier, A.; Wright, P.M.; Hog, D.T.; Yabu, K.; Allu, S.R.; Fukuzaki, T.; Carlsen, P.N., et al. A platform for the discovery of new macrolide antibiotics. Nature 2016, 533, 338–345.
73. El-Gamal, M.I.; Brahim, I.; Hisham, N.; Aladdin, R.; Mohammed, H.; Bahaaeldin, A. Recent updates of carbapenem antibiotics. Eur. J. Med. Chem. 2017, 131, 185–195.
74. Fu, H.-G.; Hu, X.-X.; Li, C.-R.; Li, Y.-H.; Wang, Y.-X.; Jiang, J.-D.; Bi, C.-W.; Tang, S.; You, X.-F.; Song, D.-Q. Design, synthesis and biological evaluation of monobactams as antibacterial agents against gram-negative bacteria. Eur. J. Med. Chem. 2016, 110, 151–163.
75. Aminov, R. History of antimicrobial drug discovery: Major classes and health impact. Biochem. Pharmacol. 2017, 133, 4–19.
76. Leach, K.L.; Brickner, S.J.; Noe, M.C.; Miller, P.F. Linezolid, the first oxazolidinone antibacterial agent. Ann. N. Y. Acad. Sci. 2011, 1222, 49–54.
77. De Souza Mendes, C.; de Souza Antunes, A. Pipeline of known chemical classes of antibiotics. Antibiotics 2013, 2, 500–534.
78. Mills, S.D. When will the genomics investment pay off for antibacterial discovery? Biochem. Pharmacol. 2006, 71, 1096–102.
79. Land, M.; Hauser, L.; Jun, S.R.; Nookaew, I.; Leuze, M.R.; Ahn, T.H.; Karpinets, T.; Lund, O.; Kora, G.; Wassenaar, T., et al. Insights from 20 years of bacterial genome sequencing. Funct. Integr. Genom. 2015, 15, 141–161.
80. 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.
81. Foulkes, J. Elitra pharmaceuticals: New paradigms for antimicrobial drug discovery. Drug Discov. Today 2002, 7, S12–S15.
82. 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.
83. Brötz-Oesterhelt, H.; Sass, P. Postgenomic strategies in antibacterial drug discovery. Future Microbiol. 2010, 5, 1553–1579.
84. Fields, F.R.; Lee, S.W.; McConnell, M.J. Using bacterial genomes and essential genes for the development of new antibiotics. Biochem. Pharmacol. 2017, 134, 74–86.
85. Yokokawa, F. Recent progress on the development of novel antitubercular agents from whole cell screening hits. J. Syn. Org. Chem. Jpn. 2014, 72, 1239–1249.
86. Moloney, M.G. Natural products as a source for novel antibiotics. Trends Pharmacol. Sci. 2016, 37, 689–701.
87. Lee, J.A.; Berg, E.L. Neoclassic drug discovery: The case for lead generation using phenotypic and functional approaches. J. Biomol. Screen. 2013, 18, 1143–1155.
88. Brown, E.D.; Wright, G.D. Antibacterial drug discovery in the resistance era. Nature 2016, 529, 336.
89. Hutter, B.; Schaab, C.; Albrecht, S.; Borgmann, M.; Brunner, N.A.; Freiberg, C.; Ziegelbauer, K.; Rock, C.O.; Ivanov, I.; Loferer, H. Prediction of mechanisms of action of antibacterial compounds by gene expression profiling. Antimicrob. Agents Chemother. 2004, 48, 2838–2844.
90. Hutter, B.; Fischer, C.; Jacobi, A.; Schaab, C.; Loferer, H. Panel of Bacillus subtilis reporter strains indicative of various modes of action. Antimicrob. Agents Chemother. 2004, 48, 2588–2594.
91. Michelini, E.; Cevenini, L.; Mezzanotte, L.; Coppa, A.; Roda, A. Cell-based assays: Fuelling drug discovery. Anal. Bioanal. Chem. 2010, 398, 227–238.
92. Gilbert, I.H. Drug discovery for neglected diseases: Molecular target-based and phenotypic approaches. J. Med. Chem. 2013, 56, 7719–7726.
93. Deeks, E.D. Fexinidazole: First global approval. Drugs 2019, 79, 215–220.
94. Eder, J.; Sedrani, R.; Wiesmann, C. The discovery of first-in-class drugs: Origins and evolution. Nat. Rev. Drug Discov. 2014, 13, 577–587.
95. Butler, M.S.; Blaskovich, M.A.T.; Cooper, M.A. Antibiotics in the clinical pipeline at the end of 2015. J. Antibiot. 2016, 70, 3.
96. Wencewicz, T.A. New antibiotics from Nature’s chemical inventory. Bioorg. Med. Chem. 2016, 24, 6227–6252.
97. Singh, S.B.; Young, K.; Silver, L.L. What is an “ideal” antibiotic? Discovery challenges and path forward. Biochem. Pharmacol. 2017, 133, 63–73.
98. Cox, G.; Sieron, A.; King, A.M.; De Pascale, G.; Pawlowski, A.C.; Koteva, K.; Wright, G.D. A common platform for antibiotic dereplication and adjuvant discovery. Cell Chem. Biol. 2017, 24, 98–109.
99. Lewis, K. New approaches to antimicrobial discovery. Biochem. Pharmacol. 2017, 134, 87–98.
100. Croucher, N.J.; Thomson, N.R. Studying bacterial transcriptomes using RNA-seq. Curr. Opin. Microbiol. 2010, 13, 619–624.
101. McGettigan, P.A. Transcriptomics in the RNA-seq era. Curr. Opin. Chem. Biol. 2013, 17, 4–11.
102. Wang, Z.; Deisboeck, T.S. Mathematical modeling in cancer drug discovery. Drug Discov. Today 2014, 19, 145–150.
103. Dersch, P.; Khan, M.A.; Mühlen, S.; Görke, B. Roles of regulatory RNAs for antibiotic resistance in bacteria and their potential value as novel drug targets. Front. Microbiol. 2017, 8, 1–12.
104. Woollard, P.M.; Mehta, N.A.L.; Vamathevan, J.J.; Van Horn, S.; Bonde, B.K.; Dow, D.J. The application of next-generation sequencing technologies to drug discovery and development. Drug Discov. Today 2011, 16, 512–519.
105. Mäder, U.; Nicolas, P.; Richard, H.; Bessières, P.; Aymerich, S. Comprehensive identification and quantification of microbial transcriptomes by genome-wide unbiased methods. Curr. Opin. Biotechnol. 2011, 22, 32–41.
106. Liu, D.; Mewalal, R.; Hu, R.; Tuskan, G.A.; Yang, X. New technologies accelerate the exploration of non-coding RNAs in horticultural plants. Hortic. Res. 2017, 4, 1–8.
107. Lloyd, N.C.; Morgan, H.W.; Nicholson, B.K.; Ronimus, R.S. The composition of Ehrlich’s Salvarsan: Resolution of a century-old debate. Angew. Chem.—Int. Ed. 2005, 44, 941–944.
108. Brazas, M.D.; Hancock, R.E.W. Using microarray gene signatures to elucidate mechanisms of antibiotic action and resistance. Drug Discov. Today 2005, 10, 1245–1252.
109. Suzuki, S.; Horinouchi, T.; Furusawa, C. Prediction of antibiotic resistance by gene expression profiles. Nat. Commun. 2014, 5, 1–12.
110. Unlu, M.; Morgan, M.E.; Minden, J.S. Difference gel electrophoresis. A single gel method for detecting changes in protein extracts. Electrophoresis 1997, 18, 2071–2077.
111. Hannigan, A.; Burchmore, R.; Wilson, J.B. The optimization of protocols for proteome difference gel electrophoresis (DiGE) analysis of preneoplastic skin. J. Proteome Res. 2007, 6, 3422–3432.
112. Roe, M.R.; Griffin, T.J. Gel-free mass spectrometry-based high throughput proteomics: Tools for studying biological response of proteins and proteomes. Proteomics 2006, 6, 4678–4687.
113. Pulido, M.R.; García-Quintanilla, M.; Gil-Marqués, M.L.; McConnell, M.J. Identifying targets for antibiotic development using omics technologies. Drug Discov. Today 2016, 21, 465–472.
114. Vranakis, I.; Goniotakis, I.; Psaroulaki, A.; Sandalakis, V.; Tselentis, Y.; Gevaert, K.; Tsiotis, G. Proteome studies of bacterial antibiotic resistance mechanisms. J. Proteom. 2014, 97, 88–99.
115. Freiberg, C.; Brötz-Oesterhelt, H.; Labischinski, H. The impact of transcriptome and proteome analyses on antibiotic drug discovery. Curr. Opin. Microbiol. 2004, 7, 451–459.
116. Wenzel, M.; Bandow, J.E. Proteomic signatures in antibiotic research. Proteomics 2011, 11, 3256–3268.
117. Carneiro, D.G.; Clarke, T.; Davies, C.C.; Bailey, D. Identifying novel protein interactions: Proteomic methods, optimisation approaches and data analysis pipelines. Methods 2016, 95, 46–54.
118. Whitmore, S.E.; Lamont, R.J. Tyrosine phosphorylation and bacterial virulence. Int. J. Oral Sci. 2012, 4, 1.
119. Kobir, A.; Shi, L.; Boskovic, A.; Grangeasse, C.; Franjevic, D.; Mijakovic, I. Protein phosphorylation in bacterial signal transduction. Biochim. Biophys. Acta—Gen. Subj. 2011, 1810, 989–994.
120. Morris, M.K.; Chi, A.; Melas, I.N.; Alexopoulos, L.G. Phosphoproteomics in drug discovery. Drug Discov. Today 2014, 19, 425–432.
121. Vihervaara, T.; Suoniemi, M.; Laaksonen, R. Lipidomics in drug discovery. Drug Discov. Today 2014, 19, 164–170.
122. Sandra, K.; Sandra, P. Lipidomics from an analytical perspective. Curr. Opin. Chem. Biol. 2013, 17, 847–853.
123. Yao, J.; Rock, C.O. Bacterial fatty acid metabolism in modern antibiotic discovery. Biochim. Biophys. Acta—Mol. Cell Biol. Lipids 2017, 1862, 1300–1309.
124. Lam, S.M.; Shui, G. Lipidomics as a principal tool for advancing biomedical research. J. Genet. Genom. 2013, 40, 375–390.
125. Lindon, J.C.; Nicholson, J.K. Analytical technologies for metabonomics and metabolomics, and multi-omic information recovery. TrAC—Trends Anal. Chem. 2008, 27, 194–204.
126. Gao, P.; Xu, G. Mass-spectrometry-based microbial metabolomics: Recent developments and applications. Anal. Bioanal. Chem. 2015, 407, 669–680.
127. Nagana Gowda, G.A.; Raftery, D. Can NMR solve some significant challenges in metabolomics? J. Magn. Reson. 2015, 260, 144–160.
128. Hoerr, V.; Duggan, G.E.; Zbytnuik, L.; Poon, K.K.H.; Große, C.; Neugebauer, U.; Methling, K.; Löffler, B.; Vogel, H.J. Characterization and prediction of the mechanism of action of antibiotics through NMR metabolomics. BMC Microbiol. 2016, 16, 1–14.
129. Mitsuwan, W.; Olaya-Abril, A.; Calderón-Santiago, M.; Jiménez-Munguía, I.; González-Reyes, J.A.; Priego-Capote, F.; Voravuthikunchai, S.P.; Rodríguez-Ortega, M.J. Integrated proteomic and metabolomic analysis reveals that rhodomyrtone reduces the capsule in Streptococcus pneumoniae. Sci. Rep. 2017, 7, 1–13.
130. Chavali, A.K.; D’Auria, K.M.; Hewlett, E.L.; Pearson, R.D.; Papin, J.A. A metabolic network approach for the identification and prioritization of antimicrobial drug targets. Trends Microbiol. 2012, 20, 113–123.
131. Milshteyn, A.; Schneider, J.S.; Brady, S.F. Mining the metabiome: Identifying novel natural products from microbial communities. Chem. Biol. 2014, 21, 1211–1223.
132. Fischbach, M.A. Antibiotics from microbes: Converging to kill. Curr. Opin. Microbiol. 2009, 12, 520–527.
133. Wright, G.D. Opportunities for natural products in 21st century antibiotic discovery. Nat. Prod. Rep. 2017, 34, 694–701.
134. Singh, S.B.; Barrett, J.F. Empirical antibacterial drug discovery - Foundation in natural products. Biochem. Pharmacol. 2006, 71, 1006–1015.
135. Kealey, C.; Creaven, C.A.; Murphy, C.D.; Brady, C.B. New approaches to antibiotic discovery. Biotechnol. Lett. 2017, 39, 805–817.
136. Nichols, D.; Cahoon, N.; Trakhtenberg, E.M.; Pham, L.; Mehta, A.; Belanger, A.; Kanigan, T.; Lewis, K.; Epstein, S.S. Use of ichip for high-throughput in situ cultivation of “uncultivable” microbial species. Appl. Environ. Microbiol. 2010, 76, 2445–2450.
137. Ling, L.L.; Schneider, T.; Peoples, A.J.; Spoering, A.L.; Engels, I.; Conlon, B.P.; Mueller, A.; Schäberle, T.F.; Hughes, D.E.; Epstein, S., et al. A new antibiotic kills pathogens without detectable resistance. Nature 2015, 517, 455–459.
138. Kolter, R.; van Wezel, G.P. Goodbye to brute force in antibiotic discovery? Nat. Microbiol. 2016, 1, 15020.
139. Kolmeder, C.A.; de Vos, W.M. Metaproteomics of our microbiome—Developing insight in function and activity in man and model systems. J. Proteom. 2014, 97, 3–16.
140. Zipperer, A.; Konnerth, M.C.; Laux, C.; Berscheid, A.; Janek, D.; Weidenmaier, C.; Burian, M.; Schilling, N.A.; Slavetinsky, C.; Marschal, M., et al. Human commensals producing a novel antibiotic impair pathogen colonization. Nature 2016, 535, 511–516.
141. Donia, M.S.; Cimermancic, P.; Schulze, C.J.; Wieland Brown, L.C.; Martin, J.; Mitreva, M.; Clardy, J.; Linington, R.G.; Fischbach, M.A. A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics. Cell 2014, 158, 1402–1414.
142. Dopazo, J. Genomics and transcriptomics in drug discovery. Drug Discov. Today 2014, 19, 126–132.
143. Swinney, D.C. Phenotypic vs. target-based drug discovery for first-in-class medicines. Clin. Pharmacol. Ther. 2013, 93, 299–301.
144. Fernandes, P.; Martens, E. Antibiotics in late clinical development. Biochem. Pharmacol. 2017, 133, 152–163.
145. Farrell, L.J.; Lo, R.; Wanford, J.J.; Jenkins, A.; Maxwell, A.; Piddock, L.J.V. Revitalizing the drug pipeline: AntibioticDB, an open access database to aid antibacterial research and development. J. Antimicrob. Chemother. 2018, 73, 2284–2297.