Brief Overview of Approaches and Challenges in New Antibiotic Development: A Focus On Drug Repurposing

Overview

Journal Front Cell Infect Microbiol

Specialties Cell Biology
Infectious Diseases
Microbiology

Date 2021 Jun 3

PMID 34079770

Citations 52

Authors

Natalie K Boyd

Chengwen Teng

Christopher R Frei

Affiliations

Soon will be listed here.

Abstract

Drug repurposing, or identifying new uses for existing drugs, has emerged as an alternative to traditional drug discovery processes involving synthesis. Drugs that are currently approved or under development for non-antibiotic indications may possess antibiotic properties, and therefore may have repurposing potential, either alone or in combination with an antibiotic. They might also serve as "antibiotic adjuvants" to enhance the activity of certain antibiotics.

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References

Brown D . Antibiotic resistance breakers: can repurposed drugs fill the antibiotic discovery void?. Nat Rev Drug Discov. 2015; 14(12):821-32. DOI: 10.1038/nrd4675. View

Fiers W, Craighead M, Singh I . Teixobactin and Its Analogues: A New Hope in Antibiotic Discovery. ACS Infect Dis. 2017; 3(10):688-690. DOI: 10.1021/acsinfecdis.7b00108. View

Ashburn T, Thor K . Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov. 2004; 3(8):673-83. DOI: 10.1038/nrd1468. View

Nichols D, Cahoon N, Trakhtenberg E, Pham L, Mehta A, Belanger A . Use of ichip for high-throughput in situ cultivation of "uncultivable" microbial species. Appl Environ Microbiol. 2010; 76(8):2445-50. PMC: 2849220. DOI: 10.1128/AEM.01754-09. View

Testa C, Johnson L . A whole-cell phenotypic screening platform for identifying methylerythritol phosphate pathway-selective inhibitors as novel antibacterial agents. Antimicrob Agents Chemother. 2012; 56(9):4906-13. PMC: 3421842. DOI: 10.1128/AAC.00987-12. View

Luepke K, Suda K, Boucher H, Russo R, Bonney M, Hunt T . Past, Present, and Future of Antibacterial Economics: Increasing Bacterial Resistance, Limited Antibiotic Pipeline, and Societal Implications. Pharmacotherapy. 2016; 37(1):71-84. DOI: 10.1002/phar.1868. View

Silver L . Challenges of antibacterial discovery. Clin Microbiol Rev. 2011; 24(1):71-109. PMC: 3021209. DOI: 10.1128/CMR.00030-10. View

Fernandes P, Martens E . Antibiotics in late clinical development. Biochem Pharmacol. 2016; 133:152-163. DOI: 10.1016/j.bcp.2016.09.025. View

CHAIN E, FLOREY H, Adelaide M, GARDNER A, HEATLEY N, Jennings M . Penicillin as a chemotherapeutic agent. 1940. Clin Orthop Relat Res. 1993; (295):3-7. View

10.

Santos Aquino de Araujo R, Barbosa-Filho J, Scotti M, Scotti L, da Cruz R, Falcao-Silva V . Modulation of Drug Resistance in Staphylococcus aureus with Coumarin Derivatives. Scientifica (Cairo). 2016; 2016:6894758. PMC: 4856757. DOI: 10.1155/2016/6894758. View

11.

RICHARDS A . PRODUCTION OF PENICILLIN IN THE UNITED STATES (1941-1946). Nature. 1964; 201:441-5. DOI: 10.1038/201441a0. View

12.

Wright G . Something old, something new: revisiting natural products in antibiotic drug discovery. Can J Microbiol. 2014; 60(3):147-54. DOI: 10.1139/cjm-2014-0063. View

13.

Gengenbacher M, Dick T . Antibacterial drug discovery: doing it right. Chem Biol. 2015; 22(1):5-6. DOI: 10.1016/j.chembiol.2014.12.005. View

14.

Perlmutter J, Forbes L, Krysan D, Ebsworth-Mojica K, Colquhoun J, Wang J . Repurposing the antihistamine terfenadine for antimicrobial activity against Staphylococcus aureus. J Med Chem. 2014; 57(20):8540-62. PMC: 4207543. DOI: 10.1021/jm5010682. View

15.

Heslop E, Csimma C, Straub V, McCall J, Nagaraju K, Wagner K . The TREAT-NMD advisory committee for therapeutics (TACT): an innovative de-risking model to foster orphan drug development. Orphanet J Rare Dis. 2015; 10:49. PMC: 4417237. DOI: 10.1186/s13023-015-0258-1. View

16.

Mostaghim S, Gagne J, Kesselheim A . Safety related label changes for new drugs after approval in the US through expedited regulatory pathways: retrospective cohort study. BMJ. 2017; 358:j3837. PMC: 5588044. DOI: 10.1136/bmj.j3837. View

17.

Hwang T, Darrow J, Kesselheim A . The FDA's Expedited Programs and Clinical Development Times for Novel Therapeutics, 2012-2016. JAMA. 2017; 318(21):2137-2138. PMC: 5820715. DOI: 10.1001/jama.2017.14896. View

18.

Couto I, Costa S, Viveiros M, Martins M, Amaral L . Efflux-mediated response of Staphylococcus aureus exposed to ethidium bromide. J Antimicrob Chemother. 2008; 62(3):504-13. DOI: 10.1093/jac/dkn217. View

19.

Kardos N, Demain A . Penicillin: the medicine with the greatest impact on therapeutic outcomes. Appl Microbiol Biotechnol. 2011; 92(4):677-87. DOI: 10.1007/s00253-011-3587-6. View

20.

Jin G, Wong S . Toward better drug repositioning: prioritizing and integrating existing methods into efficient pipelines. Drug Discov Today. 2013; 19(5):637-44. PMC: 4021005. DOI: 10.1016/j.drudis.2013.11.005. View