The Analogs of Temporin-GHa Exhibit a Broader Spectrum of Antimicrobial Activity and a Stronger Antibiofilm Potential against Staphylococcus aureus
The Analogs of Temporin-GHa Exhibit a Broader Spectrum of Antimicrobial Activity and a Stronger Antibiofilm Potential against Staphylococcus aureus
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Temporin-GHa 类似物表现出更广泛的抗菌活性和更强的针对金黄色葡萄球菌的抗菌膜潜力
DOI：
10.3390/molecules24224173
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发表时间：
2019-11-01
期刊：
影响因子：
4.6
通讯作者：
Zhang, Yingxia
中科院分区：
文献类型：
--
作者：
Xie, Zhipeng;Wei, Hanqi;Zhang, Yingxia
抗生素的滥用导致了多重耐药菌的出现，这正成为人们不得不面对的一个严重的世界性问题。在我们以前的研究中，从水蛙中克隆的temporin-GHa（GHa）对革兰氏阳性菌具有抗菌活性。为了提高其治疗潜力，我们使用基于模板和数据库辅助的设计，通过将GHa两端的组氨酸替换为赖氨酸来获得三个衍生肽，其表现出比亲本肽更快、更强的杀菌活性和更宽的谱。GHaK和GHa 4K靶向细菌膜，以更快的膜损伤速率发挥其抗菌活性。衍生肽抑制金黄色葡萄球菌生物膜的初始粘附和形成，并根除成熟生物膜，表明衍生肽有效地穿透生物膜并杀灭细菌。衍生肽的治疗指数（TI）和细胞选择性指数（CSI）显著增加，这意味着衍生肽的治疗窗口更宽。具有更高活性和细胞选择性的衍生肽有可能成为治疗S.金黄色葡萄球菌感染。我们的研究还为抗菌肽的设计和开发提供了新的见解。
The abuse of antibiotics has led to the emergence of multidrug-resistant bacteria, which is becoming a serious worldwide problem people have to face. In our previous study, temporin-GHa (GHa) cloned from Hylarana guentheri showed antimicrobial activity against Gram-positive bacteria. In order to improve its therapeutic potential, we used a template-based and a database-assisted design to obtain three derived peptides by replacing the histidine at both ends of GHa with lysine, which exhibited faster and stronger bactericidal activity and a broader spectrum than the parent peptide. GHaK and GHa4K targeted to the bacterial membrane to exert their antibacterial activities at a faster membrane damage rate. The derived peptides inhibited the initial adhesion and the formation of Staphylococcus aureus biofilms, and eradicated the mature biofilms, which indicated that the derived peptides effectively penetrated the biofilm and killed bacteria. The therapeutic index (TI) and cell selectivity index (CSI) of the derived peptides increased significantly, which means a broader therapeutic window of the derived peptides. The derived peptides with improved activity and cell selectivity have the potential to be the promising candidates for the treatment of S. aureus infections. Our research also provides new insights into the design and development of antimicrobial peptides.