Over the past years, short anti-microbial peptides have drawn growing attention in the research and trade literature because they are usually capable of killing a broad spectrum of pathogens by employing unique mechanisms of action. This study aimed to evaluate the anti-bacterial effects of a previously designed peptide named PVP towards the clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) in vitro. Secondary structure, cytotoxicity, and membrane-permeabilizing effects of the peptide were also assessed. PVP had a tendency to adopt alpha-helical conformation based upon structural predictions and circular dichroism spectroscopy (in 50% trifluoroethanol). The peptide showed MIC values ranging from 1 to 16 µg/mL against 10 strains of MRSA. In contrast to ciprofloxacin and gentamicin, PVP at sub-lethal concentration (1 µg/mL) did not provoke the development of peptide resistance after 14 serial passages. Remarkably, 1 h of exposure to 4 × MBC of PVP (8 µg/mL) was sufficient for total bacterial clearance, whereas 4 × MBC of vancomycin (8 µg/mL) failed to totally eradicate bacterial cells, even after 8 h. PVP showed negligible cytotoxicity against human dermal fibroblasts at concentrations required to kill the MRSA strains. The results of flow cytometric analysis and fluorescence microscopy revealed that PVP caused bacterial membrane permeabilization, eventually culminating in cell death. Owing to the potent anti-bacterial activity, fast bactericidal kinetics, and negligible cytotoxicity, PVP has the potential to be used as a candidate antibiotic for the topical treatment of MRSA infections.

中文翻译：

---

短抗微生物肽 PVP 的抗葡萄球菌和细胞毒活性

在过去的几年里，短抗微生物肽在研究和贸易文献中引起了越来越多的关注，因为它们通常能够通过采用独特的作用机制杀死广谱病原体。本研究旨在评估先前设计的名为 PVP 的肽对体外耐甲氧西林金黄色葡萄球菌 (MRSA) 临床菌株的抗菌作用。还评估了肽的二级结构、细胞毒性和膜渗透作用。基于结构预测和圆二色光谱（在 50% 三氟乙醇中），PVP 倾向于采用 α 螺旋构象。该肽对 10 种 MRSA 菌株的 MIC 值范围为 1 到 16 µg/mL。与环丙沙星和庆大霉素相比，亚致死浓度 (1 µg/mL) 的 PVP 在 14 次连续传代后不会引起肽抗性的发展。值得注意的是，暴露于 4 × MBC 的 PVP (8 µg/mL) 1 小时足以清除细菌，而 4 × MBC 的万古霉素 (8 µg/mL) 即使在 8 小时后也未能完全根除细菌细胞。在杀死 MRSA 菌株所需的浓度下，PVP 对人皮肤成纤维细胞的细胞毒性可以忽略不计。流式细胞仪分析和荧光显微镜的结果表明，PVP 导致细菌膜透化，最终导致细胞死亡。由于有效的抗菌活性、快速的杀菌动力学和可忽略的细胞毒性，PVP 有可能用作局部治疗 MRSA 感染的候选抗生素。