Mao Yong, Niu Sufang, Xu Xin, Wang Jun, Su Yongquan, Wu Yang, Zhong Shengping
College of Ocean and Earth Sciences, Xiamen University, Xiamen, Fujian, China.
PLoS One. 2013 Dec 13;8(12):e83268. doi: 10.1371/journal.pone.0083268. eCollection 2013.
Pc-pis is a novel piscidin-like antimicrobial polypeptide that was identified in Pseudosciaena crocea. Although active against most bacteria tested, Pc-pis was inactive against Aeromonas hydrophila and Pseudomonas aeruginosa. The Pc-pis analogue Pc-pis-His was designed by adding a histidine residue at the carboxyl terminal. Pc-pis-His demonstrated a more broad-spectrum and stronger antimicrobial activity against a representative set of microorganisms and more potent antiparasitic activity against Cryptocaryon irritans trophonts than Pc-pis. The stability assay revealed that Pc-pis-His was active against Staphylococcus aureus not only in acidic (pH 5.5-7.3) and relatively low concentration monovalent cation (0-160 mM NaCl) environments but also in alkaline (pH 7.5-9.5), divalent cation (1.25-160 mM MgCl2 and 1.25-40 mM CaCl2) and high concentration monovalent cation (320-2560 mM NaCl) environments, which indicates that the added histidine residue conferred better salt-, acid- and alkali-tolerance to Pc-pis-His. Pc-pis-His also possessed the desired heat-tolerance, which was reflected by the antimicrobial activity of the peptide after being boiled for 10-60 minutes. Hemolytic activity analysis revealed that Pc-pis-His at concentrations up to 6 µM exhibited no hemolysis against human erythrocytes, with 6 µM being a concentration that is highly active against most of the microorganisms tested, although the hemolytic activity of Pc-pis-His was enhanced compared to Pc-pis. These results provide a unique, reasonable basis for designing novel piscidins with potent, broad-spectrum and stable antimicrobial activity and new insight into the future development of piscidins as potential therapeutic agents against microbial and external protozoan parasite infections.
Pc-pis是一种在大黄鱼中鉴定出的新型类杀鱼菌素抗菌多肽。尽管对大多数测试细菌有活性，但Pc-pis对嗜水气单胞菌和铜绿假单胞菌无活性。通过在羧基末端添加一个组氨酸残基设计了Pc-pis类似物Pc-pis-His。与Pc-pis相比，Pc-pis-His对一组代表性微生物表现出更广谱、更强的抗菌活性，对刺激隐核虫滋养体具有更强的抗寄生虫活性。稳定性分析表明，Pc-pis-His不仅在酸性（pH 5.5-7.3）和相对低浓度单价阳离子（0-160 mM NaCl）环境中对金黄色葡萄球菌有活性，而且在碱性（pH 7.5-9.5）、二价阳离子（1.25-160 mM MgCl2和1.25-40 mM CaCl2）和高浓度单价阳离子（320-2560 mM NaCl）环境中也有活性，这表明添加的组氨酸残基赋予了Pc-pis-His更好的耐盐、耐酸和耐碱性。Pc-pis-His还具有所需的耐热性，这通过该肽在煮沸10-60分钟后的抗菌活性得以体现。溶血活性分析表明，浓度高达6 µM的Pc-pis-His对人红细胞无溶血作用，6 µM是对大多数测试微生物具有高活性的浓度，尽管与Pc-pis相比，Pc-pis-His的溶血活性有所增强。这些结果为设计具有强效、广谱和稳定抗菌活性的新型杀鱼菌素提供了独特、合理的依据，并为杀鱼菌素作为抗微生物和外部原生动物寄生虫感染的潜在治疗剂的未来发展提供了新的见解。
