Cobalt complexes modulate plasmid conjugation in Escherichia coli and Klebsiella pneumoniae.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Anti-Infective Agents*/pharmacology ; Klebsiella Infections*/microbiology; Animals ; Agar ; Anti-Bacterial Agents/pharmacology ; beta-Lactamases/genetics ; Escherichia coli/genetics ; Klebsiella pneumoniae/genetics ; Mammals/genetics ; Microbial Sensitivity Tests ; Plasmids/genetics

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.
(© 2024. The Author(s).)

Front Microbiol. 2020 May 06;11:761. (PMID: 32435238)
Lancet. 1969 Aug 30;2(7618):448-52. (PMID: 4183901)
Front Microbiol. 2013 Mar 07;4:44. (PMID: 23471189)
Antimicrob Agents Chemother. 2012 Sep;56(9):4703-6. (PMID: 22710119)
FEMS Microbiol Rev. 2018 Nov 1;42(6):781-804. (PMID: 30085063)
Nucleic Acids Res. 2007;35(8):e64. (PMID: 17426124)
Int J Antimicrob Agents. 2010 Apr;35(4):316-21. (PMID: 20060273)
mBio. 2015 Sep 01;6(5):e01032-15. (PMID: 26330514)
Metallomics. 2019 Oct 16;11(10):1743-1752. (PMID: 31528873)
J Antimicrob Chemother. 2011 Sep;66(9):1987-91. (PMID: 21653604)
Cent Eur J Immunol. 2015;40(2):236-42. (PMID: 26557039)
Microbiol Spectr. 2018 Jan;6(1):. (PMID: 29327679)
Antimicrob Agents Chemother. 2008 Apr;52(4):1472-80. (PMID: 18268088)
Eur J Med Chem. 2008 Oct;43(10):2189-96. (PMID: 17959275)
Int J Antimicrob Agents. 2019 May;53(5):629-636. (PMID: 30685311)
Curr Opin Microbiol. 2020 Feb;53:35-43. (PMID: 32143027)
PLoS One. 2011;6(8):e23045. (PMID: 21829688)
J Bacteriol. 1970 Oct;104(1):34-44. (PMID: 4919751)
Proc Natl Acad Sci U S A. 2021 Aug 3;118(31):. (PMID: 34326267)
PLoS Genet. 2020 Apr 29;16(4):e1008750. (PMID: 32348296)
Ann N Y Acad Sci. 1971 Jun 11;182:305-11. (PMID: 4936666)
Curr Opin Infect Dis. 2016 Dec;29(6):583-594. (PMID: 27584587)
BMJ Open. 2021 Dec 14;11(12):e054971. (PMID: 34907071)
Dalton Trans. 2015 Aug 21;44(31):13796-808. (PMID: 26148776)
J Bacteriol. 1980 Sep;143(3):1466-70. (PMID: 6106013)
Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):1269-74. (PMID: 22232693)
Lancet. 2022 Feb 12;399(10325):629-655. (PMID: 35065702)
Microbiology (Reading). 2022 Jul;168(7):. (PMID: 35849537)
J Antimicrob Chemother. 2016 Aug;71(8):2118-24. (PMID: 27165784)
Microbiol Mol Biol Rev. 2009 Dec;73(4):775-808. (PMID: 19946141)
Antimicrob Agents Chemother. 2012 Jun;56(6):3376-7. (PMID: 22450980)
Curr Opin Chem Biol. 2013 Apr;17(2):189-96. (PMID: 23270779)
Front Microbiol. 2018 Nov 08;9:2618. (PMID: 30467495)
PLoS Pathog. 2019 Dec 19;15(12):e1008162. (PMID: 31856254)
Appl Environ Microbiol. 2016 Apr 18;82(9):2872-2883. (PMID: 26969701)
J Hosp Infect. 2006 Dec;64(4):313-25. (PMID: 17046102)
mSphere. 2023 Aug 24;8(4):e0017023. (PMID: 37417759)
Medchemcomm. 2019 May 8;10(5):682-692. (PMID: 31741728)
J Bacteriol. 1976 Oct;128(1):271-82. (PMID: 789333)
J Antimicrob Chemother. 2018 May 1;73(5):1121-1137. (PMID: 29370371)
Antimicrob Agents Chemother. 2010 Oct;54(10):4493-6. (PMID: 20696875)
Plasmid. 2012 Mar;67(2):174-82. (PMID: 22289895)
Microbiology (Reading). 2020 Dec;166(12):1115-1120. (PMID: 33226934)
Sci Rep. 2022 Mar 19;12(1):4752. (PMID: 35306531)
Emerg Infect Dis. 2008 Feb;14(2):195-200. (PMID: 18258110)
J Bacteriol. 1970 Jun;102(3):648-54. (PMID: 4914070)
J Ethnopharmacol. 2019 Dec 05;245:111871. (PMID: 31022566)
mBio. 2018 Feb 6;9(1):. (PMID: 29437920)
Lancet. 2016 Jan 9;387(10014):176-87. (PMID: 26603922)
Curr Opin Microbiol. 2022 Aug;68:102152. (PMID: 35504055)
Microbiol Mol Biol Rev. 2010 Sep;74(3):434-52. (PMID: 20805406)
J Antimicrob Chemother. 2017 Aug 1;72(8):2241-2248. (PMID: 28498924)
Lancet Infect Dis. 2018 Mar;18(3):318-327. (PMID: 29276051)
J Gen Microbiol. 1972 Sep;72(2):349-55. (PMID: 4562309)
Int J Antimicrob Agents. 2008 Nov;32(5):405-10. (PMID: 18718743)
Pharmaceuticals (Basel). 2010 May 26;3(6):1711-1728. (PMID: 27713325)
Front Med (Lausanne). 2019 Apr 16;6:74. (PMID: 31041313)
Metallomics. 2011 Oct;3(10):963-70. (PMID: 21804980)
PLoS One. 2016 Jan 26;11(1):e0148098. (PMID: 26812051)
Mol Membr Biol. 2005 Jan-Apr;22(1-2):51-61. (PMID: 16092524)
Antimicrob Agents Chemother. 1973 Apr;3(4):456-62. (PMID: 4597725)
Chem Sci. 2020 Feb 12;11(10):2627-2639. (PMID: 32206266)
BMC Biotechnol. 2014 Sep 25;14:84. (PMID: 25255806)
Lett Appl Microbiol. 2019 Apr;68(4):277-293. (PMID: 30811615)
mBio. 2018 Apr 24;9(2):. (PMID: 29691332)
Emerg Infect Dis. 2011 Apr;17(4):645-52. (PMID: 21470454)
Clin Microbiol Infect. 2014 Oct;20(10):O633-5. (PMID: 24476498)
mBio. 2020 Feb 25;11(1):. (PMID: 32098822)
ChemMedChem. 2021 Oct 15;16(20):3210-3221. (PMID: 34327861)

MR/V009885/1 United Kingdom MRC_ Medical Research Council

Keywords: Anti-plasmid complexes; Antimicrobial resistance (AMR); Carbapenemase; Extended-spectrum beta-lactamase (ESBL); Plasmid conjugation

9002-18-0 (Agar)
0 (Anti-Bacterial Agents)
0 (Anti-Infective Agents)
EC 3.5.2.6 (beta-Lactamases)

Date Created: 20240406 Date Completed: 20240408 Latest Revision: 20240417

20240418

PMC10998897

10.1038/s41598-024-58895-x

38582880