Biodesign Center for Molecular Design and Biomimetics, The Biodesign Institute, Arizona State University, Tempe, Arizona 85287, United States.
School of Molecular Sciences, Arizona State University, Tempe, Arizona 85287, United States.
ACS Appl Mater Interfaces. 2021 Feb 24;13(7):8082-8094. doi: 10.1021/acsami.0c22941. Epub 2021 Feb 11.
Antibiotic-resistant bacteria are a significant and growing threat to human health. Recently, two-dimensional (2D) nanomaterials have shown antimicrobial activity and have the potential to be used as new approaches to treating antibiotic resistant bacteria. In this Research Article, we exfoliate transition metal dichalcogenide (TMDC) nanosheets using synthetic single-stranded DNA (ssDNA) sequences, and demonstrate the broad-spectrum antibacterial activity of MoSe encapsulated by the T ssDNA sequence in eliminating several multidrug-resistant (MDR) bacteria. The MoSe/T is able to eradicate Gram-positive and Gram-positive at much lower concentrations than graphene-based nanomaterials. Eradication of MDR strains of methicillin-resistant (MRSA), , , , and are shown to occur at at 75 μg mL concentration of MoSe/T, and at 150 μg mL. Molecular dynamics simulations show that the thymine bases in the T sequence lie flat on the MoSe surface and can, thus, form a very good conformal coating and allow the MoSe to act as a sharp nanoknife. Electron microscopy shows the MoSe nanosheets cutting through the cell membranes, resulting in significant cellular damage and the formation of interior voids. Further assays show the change in membrane potential and reactive oxygen species (ROS) formation as mechanisms of antimicrobial activity of MoSe/T. The cellular death pathways are also examined by mRNA expression. This work shows that biocompatible TMDCs, specifically MoSe/T, is a potent antimicrobial agent against MDR bacteria and has potential for clinical settings.
耐药菌对人类健康构成重大且日益严重的威胁。最近，二维（2D）纳米材料表现出抗菌活性，并有可能被用作治疗耐药菌的新方法。在这篇研究文章中，我们使用合成的单链 DNA（ssDNA）序列剥离过渡金属二硫属化物（TMDC）纳米片，并证明了 T ssDNA 序列包裹的 MoSe 的广谱抗菌活性，可消除几种多药耐药（MDR）细菌。MoSe/T 能够在比基于石墨烯的纳米材料低得多的浓度下消除革兰氏阳性菌和革兰氏阳性菌。显示出对耐甲氧西林金黄色葡萄球菌（MRSA）、铜绿假单胞菌、大肠杆菌、肺炎克雷伯菌、鲍曼不动杆菌和金黄色葡萄球菌的 MDR 菌株的消除作用发生在 MoSe/T 的 75μg mL 浓度下，而在 150μg mL 浓度下发生。分子动力学模拟表明，T 序列中的胸腺嘧啶碱基平放在 MoSe 表面上，因此可以形成非常好的共形涂层，并使 MoSe 能够作为锋利的纳米刀。电子显微镜显示 MoSe 纳米片穿过细胞膜，导致细胞严重损伤并形成内部空洞。进一步的测定表明，膜电位的变化和活性氧（ROS）的形成是 MoSe/T 抗菌活性的机制。还通过 mRNA 表达检查细胞死亡途径。这项工作表明，生物相容性 TMDC，特别是 MoSe/T，是一种针对 MDR 细菌的有效抗菌剂，具有在临床环境中的应用潜力。
