Antibiotic discovery in the twenty-first century: Current trends and future perspectives

Journal of Antibiotics

Volumn 63, Issue 8, 2010, Pages 423-430

  Donadio, Stefano ^a   Maffioli, Sonia ^a   Monciardini, Paolo ^a   Sosio, Margherita ^a   Jabes, Daniela ^a  

^a NAICONS Srl   (Italy)

Author keywords

antibiotics; natural products; pipeline

Indexed keywords

ABYSSOMICIN; AFN 1252; ANTIBIOTIC AGENT; ANTIINFECTIVE AGENT; BAL 30072; BC 3205; BETA LACTAMASE INHIBITOR; CB 182804; CEFTAROLINE; CEFTAZIDIME; CEFTOBIPROLE; CEM 101; CEPHALOSPORIN; CXA 101; DALBAVANCIN; DAPTOMYCIN; DELAFLOXACIN; DEOXYACTAGARDINE B; GE 2270A; ICLAPRIM; LANTIBIOTIC; LINEZOLID; NATURAL PRODUCT; NEMONOXACIN; NXL 103; NXL 104; ORFAMIDE; ORITAVANCIN; PLATENSIMYCIN; PZ 601; RAMOPLANIN; RWJ 416457; THIAZOMYCIN; THIOMURACIN; THUGGACIN A; TIACUMICIN B; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANCOMYCIN; WCK 771; ZABOFLOXACIN;

ACNE; CHEMICAL MODIFICATION; CLINICAL TRIAL; CLOSTRIDIUM DIFFICILE INFECTION; DEPROTECTION REACTION; DIARRHEA; DRUG BINDING; DRUG HALF LIFE; DRUG STRUCTURE; FUTUROLOGY; HUMAN; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; RISK; SCREENING;

ANTI-BACTERIAL AGENTS; CLINICAL TRIALS AS TOPIC; DRUG DISCOVERY; DRUG EVALUATION, PRECLINICAL; HUMANS;

EID: 77956246214     PISSN: 00218820     EISSN: None     Source Type: Journal    
DOI: 10.1038/ja.2010.62     Document Type: Review

References (67)

1. 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. 6, 29-40 (2007).
2. Projan, S. J. & Bradford, P. A. Late stage antibacterial drugs in the clinical pipeline. Curr. Opin. Microbiol. 10, 441-446 (2007).
3. Theuretzbacher, U. Future antibiotics scenarios: is the tide starting to turn? Int. J. Antimicrob. 34, 15-20 (2009).
4. Demain, A. L. Microbial natural products: alive and well in 1998. Nat. Biotechnol. 16, 3-4 (1998).
5. Demain, A. L. & Adrio, J. L. Contributions of microorganisms to industrial biology. Mol. Biotechnol. 38, 41-55 (2008).
6. Demain, A. L. Prescription for an ailing pharmaceutical industry. Nat. Biotechnol. 20, 331 (2002).
7. Koehn, F. E. New strategies and methods in the discovery of natural product anti-infective agents: the mannopeptimycins. J. Med. Chem. 51, 2613-2617 (2008).
8. Souli, M., Galani, I. & Giamarellou, H. Emergence of extensively drug-resistant and pandrug resistant Gram-negative bacilli in Europe. Euro Surveill. 13, 19045 (2008).
9. Arias, C. A. & Murray, B. E. Antibiotic-resistant bugs in the 21st century-a clinical super-challenge. N. Engl. J. Med. 360, 439-443 (2009).
10. Dorr, M. B. et al. Human pharmacokinetics and rationale for once-weekly dosing of dalbavancin, a semisynthetic glycopeptide. J. Antimicrob. Chemother. 55(Suppl. 2), 25-30 (2005).
11. Noel, G. J. et al. A randomized, double-blind trial comparing ceftobiprole medocaril with vancomycin plus ceftazidime for the treatment of patients with complicated skin and skin-structure infections. Clin. Infect. Dis. 46, 647-655 (2008).
12. Eckburg, P. et al. Focus 1 and 2: randomized double-blinded, multicenter phase III trials of the efficacy and safety of ceftaroline (CPT) vs ceftriaxone (CRO) in community-acquired pneumonia (CAP). Abstracts of papers of 49th Intersci Conf on Antimicrob Agents Chemother, No. L1-345a, San Francisco (2009).
13. Bhavnani, S. M. et al. Population pharmacokinetic and Monte Carlo simulation analyses to support phase 2/3 PZ-601 (SMP-601) dosing strategies for complicated skin and skin-structure infections. Abstracts of papers of 47th Intersci Conf on Antimicrob Agents Chemother, No.40, Chicago (2007).
14. File, T. et al. A phase study comparing two doses of radezolid to linezolid in adults with uncomplicated skin and skin structure infections (uSSSI). Abstracts of papers of 48th Intersci Conf on Antimicrob Agents Chemother, No.L-1515c, Washington, DC (2008).
15. Surber, J. et al. Efficacy and safety of torezolid phosphate (torezolid) in a dose-ranging phase 2 randomized, double-blind study in patients with severe complicated skin and skin structure infections (cSSSI). Abstracts of papers of 49th Intersci Conf on Antimicrob Agents Chemother, No.L1-335, San Francisco (2009).
16. Saxton, K., Baines, S. D., Freeman, J., O'Connor, R. & Wilcox, M. H. Effects of exposure of Clostridium difficile PCR ribotypes 027 and 001 to fluoroquinolones in a human gut model. Antimicrob. Agents Chemother. 53, 412-420 (2009).
17. Biedenbach, D. J., Jones, R. N., Ivezic-Schoenfeld, Z., Paukner, S. & Novak, R. In vitro antibacterial spectrum of BC-3205, a novel pleuromutilin derivative for oral use in humans. Abstracts of papers of 49th 49th Intersci Conf on Antimicrob Agents Chemother, No.FI-1513, San Francisco (2009).
18. Karlowsky, J. A. In vitro activity of API-1252, a novel FabI inhibitor, against clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis. Antimicrob. Agents Chemother. 51, 1580-1581 (2007).
19. Schneider, T. et al. The lipopeptide antibiotic Friulimicin B inhibits cell wall biosynthesis through complex formation with bactoprenol phosphate. Antimicrob. Agents Che-mother. 53, 1610-1618 (2009).
20. Stachyra, T. et al. In vitro activity of the b-lactamase inhibitor NXL104 against KPC-2 carbapenemase and Enterobacteriaceae expressing KPC carbapenemases. J. Anti-microb. Chemother. 64, 326-329 (2009).
21. Livermore, D. M., Mushtaq, S., Warner, M., Miossec, C. & Woodford, N. NXL-104 combinations versus Enterobacteriaceae with CTX-M extended-spectrum-b- lactamases and carbapenemases. J. Antimicrob. Chemother. 62, 1053-1066 (2008).
22. Takeda, S., Nakai, T., Wakai, Y., Ikeda, F. & Hatano, K. In vitro and in vivo activities of a new cephalosporin, FR264205, against Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 51, 826-830 (2007).
23. Endimiani, A. et al. ACHN-490, a neoglycoside with potent in vitro activity against multidrug-resistant Klebsiella pneumoniae isolates. Antimicrob. Agents Chemother. 53, 4504-4507 (2009).
24. Mushtaq, S., Warner, M. & Livermore, D. Activity of the siderophore monobactam BAL30072 against multiresistant non-fermenters. J. Antimicrob. Chemother. 65, 266-270 (2010).
25. Bister, B. et al. Abyssomicin C\a polycyclic antibiotic from a marine Verrucosispora strain as an inhibitor of the p-aminobenzoic acid/ tetrahydrofolate biosynthesis pathway. Angew. Chem. Int. Ed. 43, 2574-2576 (2004).
26. Keller, S. et al. Abyssomicins G and H and atrop-Abyssomicin C from the marine Verrucosispora strain AB-18-032. J. Antibiot. 60, 391-394 (2007).
27. Steinmetz, H. et al. Thuggacins, macrolide antibiotics active against Mycobacterium tuberculosis: isolation form myxobacteria, structure elucidation, conformation analysis and biosynthesis. Chem. Eur. J. 13, 5822-5832 (2007).
28. McAlpine, J. B. et al. Microbial genomics as a guide to drug discovery and structure elucidation: ECO-02301, a novel antifungal agent, as an example. J. Nat. Prod. 68, 493-496 (2005).
29. Banskota, A. H. et al. Genomic analyses lead to novel secondary metabolites. Part 3. ECO-0501, a novel antibacterial of a new class. J. Antibiot. 59, 533-542 (2006).
30. Gross, H. et al. The genomisotopic approach: a systematic method to isolate products of orphan biosynthetic gene clusters. Chem. Biol. 14, 53-63 (2007).
31. Singh, S. B., Phillips, J. W. & Wang, J. Highly sensitive target-based whole-cell antibacterial discovery strategy by antisense RNA silencing. Curr. Opin. Drug Discov. Devel. 10, 160-166 (2007).
32. Wang, J. et al. Platensimycin is a selective FabF inhibitor with potent antibiotic properties. Nature 441, 358-361 (2006).
33. Brandi, L. et al. Specific, efficient, and selective inhibition of prokaryotic translation inhibition of prokaryotic translation initiation by a novel peptide antibiotic. Proc. Natl Acad. Sci. USA 103, 39-44 (2006).
34. Brandi, L. et al. Novel tetrapeptide inhibitors of bacterial protein synthesis produced by a Streptomyces sp. Biochemistry 45, 3692-3702 (2006).
35. Donadio, S., Monciardini, P. & Sosio, M. Approaches to discovering novel antibacterial and antifungal agents. Methods Enzymol. 458, 3-28 (2009).
36. Willey, J. M. & van der Donk, W. A. Lantibiotics: peptides with diverse structure and function. Annu. Rev. Microbiol. 61, 477-501 (2007).
37. Appleyard, A. N. et al. NVB302: a narrow spectrum antibiotic under development for the treatment of Clostridium difficile infection. Abstracts of papers of 49th Intersci Conf on Antimicrob Agents Chemother, No.F1-1517, San Francisco (2009).
38. Jabes, D. & Donadio, S. Strategies for the isolation and characterization of antibacterial lantibiotics. Methods Mol. Biol. 618, 31-45 (2010).
39. Castiglione, F. et al. Determining the structure and mode of action of microbisporicin, a potent lantibiotic active against multiresistant pathogens. Chem. Biol. 15, 22-31 (2008).
40. Jabes, D., Brunati, C., Guglierame, P. & Donadio, S. In vitro antibacterial profile of the new lantibiotic NAI-107. Abstracts of 49th Intersci Conf on Antimicrob Agents Che-mother, No.F1-1502, San Francisco (2009).
41. Maffioli, S. I. et al. Structure revision of the lantibiotic 97518. J. Nat. Prod. 79, 605-607 (2009).
42. Maffioli, S. I., Vasile, F., Potenza, D., Brunati, C. & Donadio, S. Lantibiotic carbox-yamide derivatives with enhanced antibacterial activity. WO/2010/058238 (2010).
43. Lawton, E. M., Cotter, P. D., Hill, C. & Ross, R. P. Identification of a novel two-peptide lantibiotic, haloduracin, produced by the alkaliphile Bacillus halodurans C-125. FEMS Microbiol. Lett. 267, 64-71 (2007).
44. Oman, T. J. & van der Donk, W. A. Insights into the mode of action of the two-peptide lantibiotic haloduracin. ACS Chem. Biol. 4, 865-874 (2009).
45. Dischinger, J., Joste, M., Szekat, C., Sahl, H.-G. & Bierbaum, G. Production of the novel two-peptide lantibiotic lichenicidin by Bacillus licheniformis DSM 13. PloS ONE 4, e6788 (2009).
46. Butler, M. S. Natural products to drugs: natural product-derived compounds in clinical trials. Nat. Prod. Rep. 25, 475-516 (2008).
47. Morris, R. P. et al. Ribosomally synthesized thiopeptide antibiotics targeting elongation factor Tu. J. Am. Chem. Soc. 131, 5946-5955 (2009).
48. Singh, S. B. et al. Antibacterial evaluations of thiazomycin\a potent thiazolyl peptide antibiotic from Amycolatopsis fastidiosa. J. Antibiot. 60, 565-571 (2007).
49. Zhang, C. et al. Isolation, structure, and antibacterial activity of philipimycin, a thiazolyl peptide discovered from Actinoplanes philippinensis MA7347. J. Am. Chem. Soc. 130, 12102-12110 (2008).
50. Boakes, S., Cortés, J., Appleyard, A. N., Rudd, B. A. M. & Dawson, M. J. Organization of the genes encoding the biosynthesis of actagardine and engineering of a variant generation system. Mol. Microbiol. 72, 1126-1136 (2009).
51. Acker, M. G., Bowers, A. A. & Walsh, C. T. Generation of thiocillin variants by prepeptide gene replacement and in vivo processing by Bacillus cereus. J. Am. Chem. Soc. 131, 17563-17565 (2009).
52. Kolb, H. C. & Sharpless, B. K. The growing impact of click chemistry on drug discovery. Drug Discov. Today 8, 1128-1137 (2003).
53. Pintér, G. et al. Diazo transfer-click reaction route to new, lipophilic teicoplanin and ristocetin aglycon derivatives with high antibacterial and anti-influenza virus activity: an aggregation and receptor binding study. J. Med. Chem. 52, 6053-6061 (2009).
54. Quader, S., Boyd, S. E., Jenkins, I. D. & Houston, T. A. Multisite modification of neomycin B: combined Mitsunobu and click chemistry approach. J. Org. Chem. 72, 1962-1979 (2007).
55. Tiefenbacher, K. & Mulzer, J. Synthesis of platensimycin. J. Angew. Chem. Int. Ed. 47, 2548-2555 (2008).
56. Nicolaou, K. C. et al. Total synthesis and antibacterial properties of carbaplatensimycin. J. Am. Chem. Soc. 129, 14850-14851 (2007).
57. Nicolaou, K. C. et al. Design, synthesis, and biological evaluation of platensimycin analogues with varying degrees of molecular complexity. J. Am. Chen. Soc. 130, 13110-13119 (2008).
58. Shen, H. G. et al. Synthesis and biological evaluation of platensimycin analogs. Bioorg. Med. Chem. Lett. 19, 1623-1627 (2009).
59. 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 308, 395-398 (2005).
60. Sun, C. et al. A robust platform for the synthesis of new tetracycline antibiotics. J. Am. Chem. Soc. 130, 17913-17927 (2008).
61. Ciabatti, R. et al. Synthesis and preliminary biological characterization of new semisynthetic derivatives of ramoplanin. J. Med. Chem. 50, 3077-3085 (2007).
62. Fang, X. et al. Functional and biochemical analysis of a key series of ramoplanin analogues. Bioorg. Med. Chem. Lett. 19, 6189-6191 (2009).
63. Nam, J., Shin, D., Rew, Y. & Boger, D. L. Alanine scan of [L-Dap2]ramoplanin A2 aglycon: assessment of the importance of each residue. J. Am. Chem. Soc. 129, 8747-8755 (2007).
64. He, H. Mannopeptimycins, a novel class of glycopeptides antibiotics active against Gram-positive bacteria. Appl. Microbiol. Biotechnol. 67, 444-452 (2005).
65. Curran, W. V. et al. Semisynthetic approaches to laspartomycin analogues. J. Nat. Prod. 70, 447-450 (2007).
66. Mariani, R. et al. Antibiotics GE23077, novel inhibitors of bacterial RNA polymerase. Part 3: chemical derivatization. Bioorg. Med. Chem. Lett. 15, 3748-3752 (2005).
67. Newman, D. J. Natural products as leads to potential drugs: an old process or the new hope for drug discovery? J. Med. Chem. 51, 2589-2599 (2008).