Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/105980
Title: Repurposing the anticancer drug cisplatin with the aim of developing novel Pseudomonas aeruginosa infection control agents
Authors: Yuan, Mingjun
Chua, Song Lin
Liu, Yang
Drautz-Moses, Daniela Isabel
Yam, Joey Kuok Hoong
Aung, Thet Tun
Beuerman, Roger W.
Salido, May Margarette Santillan
Schuster, Stephan Christoph
Tan, Choon-Hong
Givskov, Michael
Yang, Liang
Nielsen, Thomas Eiland
Keywords: Cisplatin
DRNTU::Science::Biological sciences
Biofilm
Issue Date: 2018
Source: Yuan, M., Chua, S. L., Liu, Y., Drautz-Moses, D. I., Yam, J. K. H., Aung, T. T., ... Nielsen, T. E. (2018). Repurposing the anticancer drug cisplatin with the aim of developing novel Pseudomonas aeruginosa infection control agents. Beilstein Journal of Organic Chemistry, 14, 3059-3069. doi:10.3762/bjoc.14.284
Series/Report no.: Beilstein Journal of Organic Chemistry
Abstract: Antibiotic resistance threatens effective treatment of microbial infections globally. This situation has spurred the hunt for new antimicrobial compounds in both academia and the pharmaceutical industry. Here, we report how the widely used antitumor drug cisplatin may be repurposed as an effective antimicrobial against the nosocomial pathogen Pseudomonas aeruginosa. Cisplatin was found to effectively kill strains of P. aeruginosa. In such experiments, transcriptomic profiling showed upregulation of the recA gene, which is known to be important for DNA repair, implicating that cisplatin could interfere with DNA replication in P. aeruginosa. Cisplatin treatment significantly repressed the type III secretion system (T3SS), which is important for the secretion of exotoxins. Furthermore, cisplatin was also demonstrated to eradicate in vitro biofilms and in vivo biofilms in a murine keratitis model. This showed that cisplatin could be effectively used to eradicate biofilm infections which were otherwise difficult to be treated by conventional antibiotics. Although cisplatin is highly toxic for humans upon systemic exposure, a low toxicity was demonstrated with topical treatment. This indicated that higher-than-minimal inhibitory concentration (MIC) doses of cisplatin could be topically applied to treat persistent and recalcitrant P. aeruginosa infections.
URI: https://hdl.handle.net/10356/105980
http://hdl.handle.net/10220/47416
ISSN: 1860-5397
DOI: 10.3762/bjoc.14.284
Rights: © 2018 Yuan et al.; licensee Beilstein-Institut. This is an Open Access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0). Please note that the reuse, redistribution and reproduction in particular requires that the authors and source are credited. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (https://www.beilstein-journals.org/bjoc)
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles
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