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Colloidal copper oxide nanoparticles leading to a biphasic dose-response in growth inhibition of Staphylococcus aureus

Laboratory of Food, Drug, & Cosmetics, School of Health Sciences, University of Brasilia, Brasilia, 70910-900, Brazil

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Jefferson MS Lopes

Department of Physics, Federal University of Roraima, Boa Vista, 69310-000, Brazil

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Leonardo G Paterno

Laboratory of Research on Polymers & Nanomaterials, Institute of Chemistry, Brasilia, Brasília, 70904-970, Brazil

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Pérola O Magalhães

Laboratory of Natural Products, Faculty of Health Science, University of Brasilia, Brasilia, 70910-900, Brazil

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Marcílio Cunha-Filho

Laboratory of Food, Drug, & Cosmetics, School of Health Sciences, University of Brasilia, Brasilia, 70910-900, Brazil

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Guilherme M Gelfuso

Laboratory of Food, Drug, & Cosmetics, School of Health Sciences, University of Brasilia, Brasilia, 70910-900, Brazil

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Taís Gratieri

*Author for correspondence:

E-mail Address: tgratieri@gmail.com

Laboratory of Food, Drug, & Cosmetics, School of Health Sciences, University of Brasilia, Brasilia, 70910-900, Brazil

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Published Online:19 May 2023https://doi.org/10.2217/fmb-2022-0250

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Abstract

Aim: The dose response in growth inhibition of Staphylococcus aureus treated with colloidal copper oxide nanoparticles (CuO-NP) was evaluated. Methods: An in vitro microbial viability assay was conducted with CuO-NP concentrations spreading over the 0.4–848.0 μg/ml range. The dose–response curve was modeled with a double Hill equation. UV-Visible absorption and photoluminescence spectroscopies allowed tracking concentration-dependent modifications in CuO-NP. Results: Two specific phases separated by the critical concentration of 26.5 μg/ml were observed in the dose–response curve, with each exhibiting proper IC₅₀ parameters, Hill coefficients and relative amplitudes. Spectroscopy techniques reveal the occurrence of a concentration-triggered aggregation of CuO-NP starting from this critical concentration. Conclusion: The findings demonstrate a dose-related change in S. aureus sensitivity to CuO-NP, which probably arises from the aggregation of this agent.

Plain language summary

Antibacterial agents are often used to stop the growth of bacteria such as Staphylococcus aureus (S. aureus). Copper oxide nanoparticles (CuO-NP) stand as a promising candidate for this purpose. Generally, the agent´s effectiveness is inspected following a dose-response curve in which de agent´s antibacterial response is plotted against its dose (concentration). In this work, employing an extended mathematical interpretation we were capable of discerning experimentally the existence of two stages of dose-response (biphasic dose-response) in the treatment of S. aureus with CuO-NP. These results in combination with insights from spectroscopic techniques lead to the understanding that the biphasic behavior arises from the aggregation of CuO-NP at high concentrations. Therefore, according to the adopted concentration to treat S. aureus, the agent can behave as a dispersed nanoparticle or as an aggregated nanoparticle. In summary, understanding whether antibacterial agents transform as a function of concentration is important in determining their practical applications.

Tweetable abstract

Aggregation of copper oxide nanoparticles leads Staphylococcus aureus to follow a biphasic dose response in in vitro viability assay.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 18, No. 8

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History

Received 28 October 2022

Accepted 6 March 2023

Published online 19 May 2023

Published in print May 2023

Information

Keywords

Author contributions

SRS Ferreira: Writing – original draft, experimental investigation, data curation, formal analysis, validation and methodology. JMS Lopes: Writing – original draft, writing – review and editing, experimental investigation, data curation, formal analysis, validation and methodology. LG Paterno: Writing – review and editing, data curation, formal analysis, resources and validation. PO Magalhães: writing – review and editing, data curation, formal analysis, resources and validation. M Cunha-Filho: writing – review and editing, data curation, formal analysis, resources, validation and funding acquisition. GM Gelfuso: writing - review and editing, data curation, formal analysis, resources, validation and funding acquisition. T Gratieri: writing – original draft, writing – review and editing, investigation, data curation, validation, formal analysis, methodology, supervision, resources, funding acquisition and project administration.

Financial & competing interests disclosure

The authors acknowledge the Brazilian funding agency Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil, (grant no. 402587/2021-9), the University of Brasília (Edital DPI/DPG 03/2022), the Federal District Research Support Foundation (FAP-DF, Brazil, grant no. 00193-00000746/2021-08, FAP-DF, Brazil, grant no. 00193-00000802/2021-04) and Coordination for the Improvement of Higher Education Personnel (Brazil). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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