Department of Biochemical Science and Technology, National Taiwan University, 1 Roosevelt Road, Section 4, Taipei 10617, Taiwan.
Peptides. 2013 Jun;44:139-48. doi: 10.1016/j.peptides.2013.04.004. Epub 2013 Apr 15.
Antimicrobial peptides (AMPs) were recently determined to be potential candidates for treating drug-resistant bacterial infections. The aim of this study was to develop shorter AMP fragments that combine maximal bactericidal effect with minimal synthesis cost. We first synthesized a series of truncated forms of AMPs (anti-lipopolysaccharide factor from shrimp, epinecidin from grouper, and pardaxin from Pardachirus marmoratus). The minimum inhibitory concentrations (MICs) of modified AMPs against ten bacterial species were determined. We also examined the synergy between peptide and non-peptide antibiotics. In addition, we measured the inhibitory rate of cancer cells treated with AMPs by MTS assay. We found that two modified antibacterial peptides (epinecidin-8 and pardaxin-6) had a broad range of action against both gram-positive and gram-negative bacteria. Furthermore, epinecidin and pardaxin were demonstrated to have high antibacterial and anticancer activities, and both AMPs resulted in a significant synergistic improvement in the potencies of streptomycin and kanamycin against methicillin-resistant Staphylococcus aureus. Neither AMP induced significant hemolysis at their MICs. In addition, both AMPs inhibited human epithelial carcinoma (HeLa) and fibrosarcoma (HT-1080) cell growth. The functions of these truncated AMPs were similar to those of their full-length equivalents. In conclusion, we have successfully identified shorter, inexpensive fragments with maximal bactericidal activity. This study also provides an excellent basis for the investigation of potential synergies between peptide and non-peptide antibiotics, for a broad range of antimicrobial and anticancer activities.
抗菌肽(AMPs)最近被确定为治疗耐药性细菌感染的潜在候选药物。本研究旨在开发具有最大杀菌效果和最小合成成本的短抗菌肽片段。我们首先合成了一系列 AMP 的截断形式(虾抗脂多糖因子、石斑鱼内啡肽和中华绒螯蟹 Pardaxin)。测定了修饰 AMP 对十种细菌的最小抑菌浓度(MIC)。我们还研究了肽和非肽抗生素之间的协同作用。此外,我们通过 MTS 测定法测量了 AMP 处理的癌细胞的抑制率。我们发现两种修饰的抗菌肽(epinecidin-8 和 pardaxin-6)对革兰氏阳性和革兰氏阴性菌均具有广泛的作用。此外,内啡肽和 Pardaxin 具有很高的抗菌和抗癌活性,并且 AMP 使链霉素和卡那霉素对耐甲氧西林金黄色葡萄球菌的效力显著协同提高。在其 MIC 下,两种 AMP 均未引起明显溶血。此外,两种 AMP 均抑制人上皮癌细胞(HeLa)和纤维肉瘤细胞(HT-1080)的生长。这些截断 AMP 的功能与全长等效物相似。总之,我们成功地鉴定了具有最大杀菌活性的更短、更廉价的片段。这项研究还为研究肽和非肽抗生素之间的潜在协同作用提供了极好的基础,具有广泛的抗菌和抗癌活性。