Antibiotic resistance represents a tremendous contemporary clinical challenge. Given this challenge, antimicrobial peptides (AMPs) are regarded as one of the most promising new options for next-generation lead antibiotics. Here, we describe the antibacterial activities of a cationic peptide named DRP-AC4, obtained from frog skin secretion using shotgun cloning. Two modified peptides were derived by substituting the sequence of amino acids to complete the hydrophobic face (DRP-AC4b) and increase net charge (DRP-AC4a), respectively. The activity and cytotoxicity of these two peptides were compared. DRP-AC4a displayed significantly increased potency against bacteria compared to the natural peptide. It should be noted, however, that both analogue peptides demonstrated higher lytic ability than the natural peptide against the membranes of mammalian erythrocytes. At the same time, all three peptides displayed lower hemolytic activity compared to their antibacterial activity. Here, we demonstrate that AMPs have more complex activity mechanisms and faster bactericidal rates than traditional antibiotics, which may be one of the reasons why bacteria do not develop resistance to them. These discoveries provide interesting insights into the discovery and development of novel drugs from natural sources.

中文翻译：

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从红眼树蛙Agalychnis callidryas的皮肤分泌物中鉴定和设计新型抗菌肽Dermaseptin-AC。

抗生素耐药性代表着巨大的当代临床挑战。面对这一挑战，抗菌肽（AMPs）被视为下一代先导抗生素的最有希望的新选择之一。在这里，我们描述了使用shot弹枪克隆从青蛙皮肤分泌物中获得的名为DRP-AC4的阳离子肽的抗菌活性。通过修饰氨基酸序列分别完成疏水表面（DRP-AC4b）和增加净电荷（DRP-AC4a），得到了两个修饰的肽。比较了这两种肽的活性和细胞毒性。与天然肽相比，DRP-AC4a对细菌的效力显着提高。但应注意，这两种类似的肽都比天然肽具有更高的针对哺乳动物红细胞膜的裂解能力。同时，所有三种肽均显示出比其抗菌活性更低的溶血活性。在这里，我们证明了AMPs比传统抗生素具有更复杂的活性机制和更快的杀菌速度，这可能是细菌不对它们产生抗药性的原因之一。这些发现为从自然资源中发现和开发新药提供了有趣的见解。这可能是细菌不对细菌产生抗性的原因之一。这些发现为从自然资源中发现和开发新药提供了有趣的见解。这可能是细菌不对细菌产生抗性的原因之一。这些发现为从自然资源中发现和开发新药提供了有趣的见解。