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Alav, Ilyas, Pordelkhaki, Parisa, de Resende, Pedro Ernesto, Partington, Hannah, Gibbons, Simon, Lord, Rianne M. 
ORCID: https://orcid.org/0000-0001-9981-129X and Buckner, Michelle M. C.
(2024)
Cobalt complexes modulate plasmid conjugation in Escherichia coli and Klebsiella pneumoniae.
Scientific Reports, 14.
ISSN 2045-2322
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Abstract
Antimicrobial resistance genes (ARG), such as extended-spectrum β-lactamase (ESBL) and carbapenemase genes, are commonly carried on plasmids. Plasmids can transmit between bacteria, disseminate globally, and cause clinically important resistance. Therefore, targeting plasmids could reduce ARG prevalence, and restore the efficacy of existing antibiotics. Cobalt complexes possess diverse biological activities, including antimicrobial and anticancer properties. However, their effect on plasmid conjugation has not been explored yet. Here, we assessed the effect of four previously characterised bis(N-picolinamido)cobalt(II) complexes lacking antibacterial activity on plasmid conjugation in Escherichia coli and Klebsiella pneumoniae. Antimicrobial susceptibility testing of these cobalt complexes confirmed the lack of antibacterial activity in E. coli and K. pneumoniae. Liquid broth and solid agar conjugation assays were used to screen the activity of the complexes on four archetypical plasmids in E. coli J53. The cobalt complexes significantly reduced the conjugation of RP4, R6K, and R388 plasmids, but not pKM101, on solid agar in E. coli J53. Owing to their promising activity, the impact of cobalt complexes was tested on the conjugation of fluorescently tagged extended-spectrum β-lactamase encoding pCTgfp plasmid in E. coli and carbapenemase encoding pKpQILgfp plasmid in K. pneumoniae, using flow cytometry. The complexes significantly reduced the conjugation of pKpQILgfp in K. pneumoniae but had no impact on pCTgfp conjugation in E. coli. The cobalt complexes did not have plasmid-curing activity, suggesting that they target conjugation rather than plasmid stability. To our knowledge, this is the first study to report reduced conjugation of clinically relevant plasmids with cobalt complexes. These cobalt complexes are not cytotoxic towards mammalian cells and are not antibacterial, therefore they could be optimised and employed as inhibitors of plasmid conjugation.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Information: I.A. and M.M.C.B. were funded by the MRC grant MR/V009885/1 (New Investigator Research Grant to M.M.C.B.). H.P. was funded by a Frank Kerr undergraduate research award. R.M.L. was funded by the University of East Anglia start-up and the UKRI FLF MR/T041315/1. |
| Uncontrolled Keywords: | anti-plasmid complexes,antimicrobial resistance (amr),carbapenemase,extended-spectrum beta-lactamase (esbl),plasmid conjugation |
| Faculty \ School: | Faculty of Science > School of Pharmacy (former - to 2024) Faculty of Science > School of Chemistry, Pharmacy and Pharmacology |
| UEA Research Groups: | Faculty of Science > Research Centres > Centre for Molecular and Structural Biochemistry Faculty of Science > Research Groups > Chemistry of Life Processes Faculty of Science > Research Groups > Chemistry of Materials and Catalysis |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 02 Sep 2024 13:30 |
| Last Modified: | 14 Oct 2024 00:01 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/96419 |
| DOI: | 10.1038/s41598-024-58895-x |
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