and are associated with life-threatening infections. Despite the best medical care, these infections frequently occur due to antibiotic resistance and the formation of biofilms of these two bacteria (i.e., clusters of bacteria embedded in a matrix). As a consequence, there is an urgent need for effective anti-biofilm treatments. Here, we describe the antibacterial properties of a combination treatment of diethyldithiocarbamate (DDC) and copper ions (Cu) and their low toxicity and . The antibacterial activity of DDC and Cu was assessed against both planktonic and biofilm cultures of and using viability assays, microscopy, and attachment assays. Cytotoxicity of DDC and Cu (DDC-Cu) was determined using a human fibroblast cell line. antimicrobial activity and toxicity were monitored in larvae. DDC-Cu concentrations of 8 μg/ml DDC and 32 μg/ml Cu resulted in over 80% MRSA and biofilm killing, showed synergistic and additive effects in both planktonic and biofilm cultures of and , and synergized multiple antibiotics. DDC-Cu inhibited MRSA and attachment and biofilm formation in the xCELLigence and Bioflux systems. and toxicity of DDC, Cu and DDC-Cu resulted in > 70% fibroblast viability and > 90% survival. Treatment with DDC-Cu significantly increased the survival of infected larvae (87% survival of infected, treated larvae . 47% survival of infected, untreated larvae, < 0.001). Therefore, DDC-Cu is a promising new antimicrobial with activity against planktonic and biofilm cultures of and and low cytotoxicity . This gives us high confidence to progress to mammalian animal studies, testing the antimicrobial efficacy and safety of DDC-Cu.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9500474 | PMC |
http://dx.doi.org/10.3389/fmicb.2022.999893 | DOI Listing |
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