Issue 10, 2018

Unexpected insights into antibacterial activity of zinc oxide nanoparticles against methicillin resistant Staphylococcus aureus (MRSA)

Abstract

Zinc oxide nanoparticles (ZnO-NPs) are attractive as broad-spectrum antibiotics, however, their further engineering as antimicrobial agents and clinical translation is impeded by controversial data about their mechanism of activity. It is commonly reported that ZnO-NP's antimicrobial activity is associated with the production of reactive oxygen species (ROS). Here we disprove this concept by comparing the antibacterial potency of ZnO-NPs and their capacity to generate ROS with hydrogen peroxide (H2O2). Then, using gene transcription microarray analysis, we provide evidence for a novel toxicity mechanism. Exposure to ZnO-NPs resulted in over three-log reduction in colonies of methicillin resistant S. aureus with minimal increase in ROS or lipid peroxidation. The amount of ROS required for the same amount of killing by H2O2 was much greater than that generated by ZnO-NPs. In contrast to H2O2, ZnO-NP mediated killing was not mitigated by the antioxidant, N-acetylcysteine. ZnO-NPs caused significant up-regulation of pyrimidine biosynthesis and carbohydrate degradation. Simultaneously, amino acid synthesis in S. aureus was significantly down-regulated indicating a complex mechanism of antimicrobial action involving multiple metabolic pathways. The results of this study point to the importance of specific experimental controls in the interpretation of antimicrobial mechanistic studies and the need for targeted molecular mechanism studies. Continued investigation on the antibacterial mechanisms of biomimetic ZnO-NPs is essential for future clinical translation.

Graphical abstract: Unexpected insights into antibacterial activity of zinc oxide nanoparticles against methicillin resistant Staphylococcus aureus (MRSA)

Supplementary files

Article information

Article type
Paper
Submitted
14 11月 2017
Accepted
15 2月 2018
First published
16 2月 2018

Nanoscale, 2018,10, 4927-4939

Unexpected insights into antibacterial activity of zinc oxide nanoparticles against methicillin resistant Staphylococcus aureus (MRSA)

U. Kadiyala, E. S. Turali-Emre, J. H. Bahng, N. A. Kotov and J. S. VanEpps, Nanoscale, 2018, 10, 4927 DOI: 10.1039/C7NR08499D

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements