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Possible involvement of ROS generation in vorinostat pretreatment induced enhancement of the antibacterial activity of ciprofloxacin

Authors Masadeh MM, Alzoubi KH, Al-azzam SI, Al-buhairan AM

Received 6 August 2017

Accepted for publication 12 September 2017

Published 17 October 2017 Volume 2017:9 Pages 119—124


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Arthur Frankel

Majed M Masadeh,1 Karem H Alzoubi,2 Sayer I Al-azzam,2 Ahlam M Al-buhairan3

1Department of Pharmaceutical Technology, 2Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Clinical Laboratory Sciences, King Saud University, Riyadh, Saudi Arabia

Abstract: The mechanism underlying ciprofloxacin action involves interference with transcription and replication of bacterial DNA and, thus, the induction of double-strand breaks in DNA. It also involves elevated oxidative stress, which might contribute to bacterial cell death. Vorinostat was shown to induce oxidative DNA damage. The current work investigated a possible interactive effect of vorinostat on ciprofloxacin-induced cytotoxicity against a number of reference bacteria. Standard bacterial strains were Escherichia coli ATCC 35218, Staphylococcus aureus ATCC29213, Pseudomonas aeruginosa ATCC 9027, Staphylococcus epidermidis ATCC 12228, Acinetobacter baumannii ATCC 17978, Proteus mirabilis ATCC 12459, Klebsiella pneumoniae ATCC 13883, methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43300), and Streptococcus pneumoniae (ATCC 25923). The antibacterial activity of ciprofloxacin, with or without pretreatment of bacterial cells by vorinostat, was examined using the disc diffusion procedure and determination of the minimum inhibitory concentration (MIC) and zones of inhibition of bacterial growth. All tested bacterial strains showed sensitivity to ciprofloxacin. When pretreated with vorinostat, significantly larger zones of inhibition and smaller MIC values were observed in all bacterial strains compared to those treated with ciprofloxacin alone. In correlation, generation of reactive oxygen species (ROS) induced by the antibacterial action of ciprofloxacin was enhanced by treatment of bacterial cells with vorinostat. Results showed the possible agonistic properties of vorinostat when used together with ciprofloxacin. This could be related to the ability of these agents to enhance oxidative stress in bacterial cells.

Keywords: flouroquinolones, MIC, histone deacetylase inhibitor, oxidative stress, antimicrobial susceptibility

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