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

Li, Fangfei, Harry, Elizabeth J., Bottomley, Amy L., Edstein, Michael D., Birrell, Geoffrey W., Woodward, Clifford E., Keene, F. Richard, and Collins, J. Grant (2014) Dinuclear ruthenium(II) antimicrobial agents that selectively target polysomes in vivo. Chemical Science, 5 (2). pp. 685-693.

[img]
Preview
PDF (Published Version) - Published Version
Available under License Creative Commons Attribution Non-commercial.

Download (1MB)
View at Publisher Website: http://dx.doi.org/10.1039/c3sc52166d
 
34
88


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.

Item ID: 30380
Item Type: Article (Research - C1)
ISSN: 2041-6539
Keywords: antimicrobial, florescence microscopy, dinuclear ruthenim complex, ribosome, RNA
Additional Information:

This is an open access article published under a CC-BY-NC 3.0 license.

Funders: Australian Research Council (ARC)
Projects and Grants: ARC grant DP0987178
Date Deposited: 27 Nov 2013 07:36
FoR Codes: 03 CHEMICAL SCIENCES > 0302 Inorganic Chemistry > 030201 Bioinorganic Chemistry @ 25%
11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110801 Medical Bacteriology @ 75%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970103 Expanding Knowledge in the Chemical Sciences @ 20%
97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 20%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 60%
Downloads: Total: 88
Last 12 Months: 33
More Statistics

Actions (Repository Staff Only)

Item Control Page Item Control Page