Repurposing the anticancer drug cisplatin with the aim of developing novel Pseudomonas aeruginosa infection control agents
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Repurposing the anticancer drug cisplatin with the aim of developing novel Pseudomonas aeruginosa infection control agents. / Yuan, Mingjun; Chua, Song Lin; Liu, Yang; Drautz-Moses, Daniela I.; Hoong Yam, Joey Kuok; Aung, Thet Tun; Beuerman, Roger W.; Santillan Salido, May Margarette; Schuster, Stephan C.; Tan, Choon Hong; Givskov, Michael; Yang, Liang; Nielsen, Thomas E.
In: Beilstein Journal of Organic Chemistry, Vol. 14, 2018, p. 3059-3069.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Repurposing the anticancer drug cisplatin with the aim of developing novel Pseudomonas aeruginosa infection control agents
AU - Yuan, Mingjun
AU - Chua, Song Lin
AU - Liu, Yang
AU - Drautz-Moses, Daniela I.
AU - Hoong Yam, Joey Kuok
AU - Aung, Thet Tun
AU - Beuerman, Roger W.
AU - Santillan Salido, May Margarette
AU - Schuster, Stephan C.
AU - Tan, Choon Hong
AU - Givskov, Michael
AU - Yang, Liang
AU - Nielsen, Thomas E.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Biofilm
KW - Cisplatin
KW - Pseudomonas aeruginosa
KW - Resistance
KW - Type III secretion
U2 - 10.3762/bjoc.14.284
DO - 10.3762/bjoc.14.284
M3 - Journal article
C2 - 30591828
AN - SCOPUS:85059320589
VL - 14
SP - 3059
EP - 3069
JO - Beilstein Journal of Organic Chemistry
JF - Beilstein Journal of Organic Chemistry
SN - 2195-951X
ER -
ID: 212854409