Dinuclear polypyridylruthenium(II) complexes: flow cytometry studies of their accumulation in bacteria and the effect on the bacterial membrane

Fangfei Li, Marshall Feterl, Jeffrey M. Warner, F. Richard Keene*, J. Grant Collins

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

34 Citations (Scopus)

Abstract

Objectives: To determine the energy dependency of and the contribution of the membrane potential to the cellular accumulation of the dinuclear complexes [{Ru(phen)2}2{μ-bbn}]4+ (Rubbn) and the mononuclear complexes [Ru(Me4phen)3]2+ and [Ru(phen)2(bb7)]2+ in Staphylococcus aureus and Escherichia coli, and to examine their effect on the bacterial membrane.

Methods: The accumulation of the ruthenium complexes in bacteria was determined using flow cytometry at a range of temperatures. The cellular accumulation of the ruthenium complexes was also determined in cells that had been incubated with the metal complexes in the presence or absence of metabolic stimulators or inhibitors and/or commercial dyes to determine the membrane potential or membrane permeability.

Results: The accumulation of ruthenium complexes in the two bacterial strains was shown to increase with increasing incubation temperature, with the relative increase in accumulation greater with E. coli, particularly for Rubb12 and Rubb16. No decrease in accumulation was observed for Rubb12 in ATP-inhibited cells. While carbonyl cyanide m-chlorophenyl hydrazone (CCCP) did depolarize the cell membrane, no reduction in the accumulation of Rubb12 was observed; however, all ruthenium complexes, when incubated with S. aureus at concentrations twice their MIC, depolarized the membrane to a similar extent to CCCP. Except for the mononuclear complex [Ru(Me4phen)3]2+, incubation of any of the other ruthenium complexes allowed a greater quantity of the membrane-impermeable dye TO-PRO-3 to be taken up by S. aureus.

Conclusions: The results indicate that the potential new antimicrobial Rubbn complexes enter the cell in an energy-independent manner, depolarize the cell membrane and significantly permeabilize the cellular membrane.
Original languageEnglish
Pages (from-to)2825–2833
JournalJournal of Antimicrobial Chemotherapy
Volume68
Issue number12
DOIs
Publication statusPublished - 1 Dec 2013
Externally publishedYes

User-Defined Keywords

  • bactericidal metal complexes
  • cellular accumulation
  • membrane depolarization
  • membrane permeability

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