Dinuclear ruthenium(II) antimicrobial agents that selectively target polysomes in vivo

Fangfei Li, Elizabeth J. Harry, Amy L. Bottomley, Michael D. Edstein, Geoffrey W Birrell, Clifford E. Woodward, F. Richard Keene*, J. Grant Collins*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

54 Citations (Scopus)

Abstract

Wide-field fluorescence microscopy at high magnification was used to study the intracellular binding site of Rubb16 in Escherichia coli. Upon incubation of E. coli cells at the minimum inhibitory concentration, Rubb16 localised at ribosomes with no significant DNA binding observed. Furthermore, Rubb16 condensed the ribosomes when they existed as polysomes. It is postulated that the condensation of polysomes would halt protein production, and thereby inhibit bacterial growth. The results of this study indicate that the family of inert dinuclear ruthenium complexes Rubbn selectively target RNA over DNA in vivo. Selective RNA targeting could be advantageous for the development of therapeutic agents, and because of differences in ribosome structure between bacteria and eukaryotic cells, the Rubbn complexes could be selectively toxic to bacteria. In support of this hypothesis, the toxicity of Rubb16 was found to be significantly less to liver and kidney cell lines than against a range of bacteria.
Original languageEnglish
Pages (from-to)685-693
Number of pages9
JournalChemical Science
Volume5
Issue number2
DOIs
Publication statusPublished - 25 Nov 2013

Fingerprint

Dive into the research topics of 'Dinuclear ruthenium(II) antimicrobial agents that selectively target polysomes in vivo'. Together they form a unique fingerprint.

Cite this