Antimicrobial activity and antibiotic synergy of a biphosphinic ruthenium complex against clinically relevant bacteria

Abstract

The aim of this study was to investigate the antibacterial activity, antibiotic-associated synergy, and anti-biofilm activity of the ruthenium complex, cis-[RuCl₂ (dppb) (bqdi)]²⁺ (RuNN). RuNN exhibited antimicrobial activity against Gram-positive bacteria with minimum inhibitory concentration (MIC) values ranging from 15.6 to 62.5 µg ml⁻¹ and minimum bactericidal concentration (MBC) values ranging from 62.5 to 125 µg ml⁻¹. A synergistic effect against Staphylococcus spp. was observed when RuNN was combined with ampicillin, and the range of associated fractional inhibitory concentration index (FICI) values was 0.187 to 0.312. A time-kill curve indicated the bactericidal activity of RuNN in the first 1–5 h. In general, RuNN inhibited biofilm formation and disrupted mature biofilms. Furthermore, RuNN altered the cellular morphology of S. aureus biofilms. Further, RuNN did not cause hemolysis of erythrocytes. The results of this study provide evidence that RuNN is a novel therapeutic candidate to treat bacterial infections caused by Staphylococcus biofilms.

Keywords:

• Metallodrugs
• ruthenium
• antimicrobial activity
• synergistic effect
• biofilm

Acknowledgements

The authors would like to thank Editage (www.editage.com) for English language editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Fundação Cearense de Apoio ao Desenvolvimento Cientifico e Tecnológico (FUNCAP), Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), the Central Analítica-UFC/CT-INFRA/MCTI-SISNANO/Pro-Equipamentos CAPES. In addition, E.H.S.S. (CNPq researcher fellowship #308383/2018-4, Universal 403866/2016-2), and L.G.F.L. (CNPq researcher fellowship #303355/2018-2, PRONEX PR2 0101-00030.01.00/15, and CAPES (23038.008968/2012-87), are grateful to CNPq, FUNCAP, and CAPES.