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Copper(II)-Bis(Thiosemicarbazonato) Complexes as Antibacterial Agents: Insights into Their Mode of Action and Potential as Therapeutics

Djoko, Karrera Y.; Goytia, Maira M.; Donnelly, Paul S.; Schembri, Mark A.; Shafer, William M.; McEwan, Alastair G.

Copper(II)-Bis(Thiosemicarbazonato) Complexes as Antibacterial Agents: Insights into Their Mode of Action and Potential as Therapeutics Thumbnail


Authors

Maira M. Goytia

Paul S. Donnelly

Mark A. Schembri

William M. Shafer

Alastair G. McEwan



Abstract

There is increasing interest in the use of lipophilic copper (Cu)-containing complexes to combat bacterial infections. In this work, we showed that Cu complexes with bis(thiosemicarbazone) ligands [Cu(btsc)] exert antibacterial activity against a range of medically significant pathogens. Previous work using Neisseria gonorrhoeae showed that Cu(btsc) complexes may act as inhibitors of respiratory dehydrogenases in the electron transport chain. We now show that these complexes are also toxic against pathogens that lack a respiratory chain. Respiration in Escherichia coli was slightly affected by Cu(btsc) complexes, but our results indicate that, in this model bacterium, the complexes act primarily as agents that deliver toxic Cu ions efficiently into the cytoplasm. Although the chemistry of Cu(btsc) complexes may dictate their mechanism of action, their efficacy depends heavily on bacterial physiology. This is linked to the ability of the target bacterium to tolerate Cu and, additionally, the susceptibility of the respiratory chain to direct inhibition by Cu(btsc) complexes. The physiology of N. gonorrhoeae, including multidrug-resistant strains, makes it highly susceptible to damage by Cu ions and Cu(btsc) complexes, highlighting the potential of Cu(btsc) complexes (and Cu-based therapeutics) as a promising treatment against this important bacterial pathogen.

Citation

Djoko, K. Y., Goytia, M. M., Donnelly, P. S., Schembri, M. A., Shafer, W. M., & McEwan, A. G. (2015). Copper(II)-Bis(Thiosemicarbazonato) Complexes as Antibacterial Agents: Insights into Their Mode of Action and Potential as Therapeutics. Antimicrobial Agents and Chemotherapy, 59(10), 6444-6453. https://doi.org/10.1128/aac.01289-15

Journal Article Type Article
Acceptance Date Jul 23, 2015
Online Publication Date Aug 3, 2015
Publication Date Oct 1, 2015
Deposit Date Sep 6, 2017
Publicly Available Date Mar 28, 2024
Journal Antimicrobial Agents and Chemotherapy
Print ISSN 0066-4804
Electronic ISSN 1098-6596
Publisher American Society for Microbiology
Peer Reviewed Peer Reviewed
Volume 59
Issue 10
Pages 6444-6453
DOI https://doi.org/10.1128/aac.01289-15

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