Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/138504
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Type: | Journal article |
Title: | In vitro and in vivo evaluation of diethyldithiocarbamate with copper ions and its liposomal formulation for the treatment of Staphylococcus aureus and Staphylococcus epidermidis biofilms |
Author: | Kaul, L. Abdo, A.I. Coenye, T. Swift, S. Zannettino, A. Süss, R. Richter, K. |
Citation: | Biofilms, 2023; 5:100130-1-100130-10 |
Publisher: | Elsevier BV |
Issue Date: | 2023 |
ISSN: | 1479-0505 2590-2075 |
Statement of Responsibility: | Laurine Kaul, Adrian I. Abdo, Tom Coenye, Simon Swift, Andrew Zannettino, Regine Süss, Katharina Richter |
Abstract: | Surgical site infections (SSIs) are mainly caused by Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis) biofilms. Biofilms are aggregates of bacteria embedded in a self-produced matrix that offers protection against antibiotics and promotes the spread of antibiotic-resistance in bacteria. Consequently, antibiotic treatment frequently fails, resulting in the need for alternative therapies. The present study describes the in vitro efficacy of the Cu(DDC)2 complex (2:1 M ratio of diethyldithiocarbamate (DDC−) and Cu2+) with additional Cu2+ against S. aureus and S. epidermidis biofilms in models mimicking SSIs and in vitro antibacterial activity of a liposomal Cu(DDC)2 + Cu2+ formulation. The in vitro activity on S. aureus and S. epidermidis biofilms grown on two hernia mesh materials and in a wound model was determined by colony forming unit (CFU) counting. Cu2+-liposomes and Cu(DDC)2-liposomes were prepared, and their antibacterial activity was assessed in vitro using the alamarBlue assay and CFU counting and in vivo using a Galleria mellonella infection model. The combination of 35 μM DDC− and 128 μM Cu2+ inhibited S. aureus and S. epidermidis biofilms on meshes and in a wound infection model. Cu(DDC)2-liposomes + free Cu2+ displayed similar antibiofilm activity to free Cu(DDC)2 + Cu2+, and significantly increased the survival of S. epidermidis-infected larvae. Whilst Cu(DDC)2 + Cu2+ showed substantial antibiofilm activity in vitro against clinically relevant biofilms, its application in mammalian in vivo models is limited by solubility. The liposomal Cu(DDC)2 + Cu2+ formulation showed antibiofilm activity in vitro and antibacterial activity and low toxicity in G. mellonella, making it a suitable water-soluble formulation for future application on infected wounds in animal trials. |
Keywords: | Surgical site infections; Diethyldithiocarbamate; Copper ions; Liposomes; Staphylococcus aureus; Staphylococcus epidermidis |
Description: | Available online 17 May 2023 |
Rights: | © 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
DOI: | 10.1016/j.bioflm.2023.100130 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/GNT1163634 http://purl.org/au-research/grants/nhmrc/2004036 |
Published version: | http://dx.doi.org/10.1016/j.bioflm.2023.100130 |
Appears in Collections: | IPAS publications Pharmacology publications Surgery publications |
Files in This Item:
File | Description | Size | Format | |
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hdl_138504.pdf | Published version | 3.24 MB | Adobe PDF | View/Open |
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