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二乙基二硫代氨基甲酸盐与铜离子的组合对[具体生物名称1]、[具体生物名称2]生物膜以及[具体生物名称3]具有活性。

The combination of diethyldithiocarbamate and copper ions is active against and biofilms and .

作者信息

Kaul Laurine, Abdo Adrian I, Coenye Tom, Krom Bastiaan P, Hoogenkamp Michel A, Zannettino Andrew C W, Süss Regine, Richter Katharina

机构信息

Richter Lab, Basil Hetzel Institute for Translational Health Research, Department of Surgery, University of Adelaide, Adelaide, SA, Australia.

Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmaceutical Sciences, University of Freiburg, Freiburg, Germany.

出版信息

Front Microbiol. 2022 Sep 9;13:999893. doi: 10.3389/fmicb.2022.999893. eCollection 2022.

Abstract

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.

摘要

[细菌名称1]和[细菌名称2]与危及生命的感染有关。尽管有最佳的医疗护理,但由于抗生素耐药性以及这两种细菌生物膜的形成(即嵌入基质中的细菌簇),这些感染仍频繁发生。因此,迫切需要有效的抗生物膜治疗方法。在此,我们描述了二乙基二硫代氨基甲酸盐(DDC)和铜离子(Cu)联合治疗的抗菌特性及其低毒性。使用活力测定、显微镜检查和附着测定,评估了DDC和Cu对[细菌名称1]和[细菌名称2]的浮游菌和生物膜培养物的抗菌活性。使用人成纤维细胞系测定了DDC和Cu(DDC-Cu)的细胞毒性。在[动物名称]幼虫中监测了抗菌活性和毒性。8μg/ml DDC和32μg/ml Cu的DDC-Cu浓度导致超过80%的耐甲氧西林金黄色葡萄球菌(MRSA)和[细菌名称2]生物膜被杀灭,在[细菌名称1]和[细菌名称2]的浮游菌和生物膜培养物中均显示出协同和相加作用,并与多种抗生素协同作用。DDC-Cu在xCELLigence和Bioflux系统中抑制了MRSA和[细菌名称2]的附着及生物膜形成。DDC、Cu和DDC-Cu的[毒性相关指标1]和[毒性相关指标2]毒性导致成纤维细胞活力>70%,[动物名称]存活率>90%。用DDC-Cu治疗显著提高了感染幼虫的存活率(感染且经治疗的幼虫存活率为87%,感染但未治疗的幼虫存活率为47%,P<0.001)。因此,DDC-Cu是一种有前景的新型抗菌剂,对MRSA和[细菌名称2]的浮游菌和生物膜培养物具有活性且细胞毒性低。这使我们有很大信心推进到哺乳动物动物研究,测试DDC-Cu的抗菌疗效和安全性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44ce/9500474/b3c5bf605b37/fmicb-13-999893-g001.jpg

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