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Antifungal Activity of Synthetic Scorpion Venom-Derived Peptide Analogues Against Candida albicans
International Journal of Peptide Research and Therapeutics ( IF 2.0 ) Pub Date : 2020-06-05 , DOI: 10.1007/s10989-020-10084-w
Sabrina S. Snyder , Jeremy W. Gleaton , Dickson Kirui , Wen Chen , Nancy J. Millenbaugh

Fungal infections are becoming a serious problem due to their high morbidity and mortality combined with the rise in drug resistance and dearth of new antimycotic drugs. The scorpion venom-derived peptide BmKn2, and its synthetic analogue Kn2–7, were previously observed to have antibacterial activity. These peptides and their d-amino acid analogues (dBmKn2 and dKn2–7) were tested for antifungal activity against drug resistant and clinical isolates of Candida albicans. In planktonic susceptibility studies, dKn2–7 had greater activity than the other three peptides against 6 out of 7 fungal strains, with no apparent correlation between drug resistance and minimum fungicidal concentrations (MFCs). Time kill experiments demonstrated that the fungicidal activity of dKn2–7 began within the first hour and killing rates were dose dependent at ≥ 1 × MFC. Against biofilms, the d-analogues were the most effective, while the l-analogues had low efficacy in most strains even at 10 times the planktonic MFC. Stability testing suggests that this increased efficacy of the d-analogues may be due to increased resistance to protease degradation compared to the l-analogues. Peptides were also assessed for mammalian cell toxicity. BmKn2 and dBmKn2 induced significant hemolysis at levels similar to their MFCs, whereas Kn2–7 and dKn2–7 caused hemolysis at 4–16 times their MFCs. The 50% inhibitory concentration (IC50) for dKn2–7 against murine fibroblasts was greater than or equal to the planktonic MFCs and biofilm IC50s for dKn2–7 in all C. albicans strains tested. These results support the potential for dKn2–7 to be further investigated as a novel antifungal therapeutic.



中文翻译:

合成蝎毒毒肽类似物对白色念珠菌的抗真菌活性。

真菌感染由于其高发病率和高死亡率以及耐药性的增加和新抗真菌药物的缺乏而成为一个严重的问题。蝎毒的肽BmKn2及其合成类似物Kn2-7先前被发现具有抗菌活性。测试了这些肽及其d-氨基酸类似物(dBmKn2和dKn2-7)对白色念珠菌的耐药性和临床分离株的抗真菌活性。在浮游易感性研究中,dKn2–7对其他7种真菌菌株中的6种具有比其他三种肽更大的活性,在耐药性和最低杀真菌浓度之间没有明显的相关性。时间杀灭实验表明,dKn2-7的杀真菌活性在第一个小时内开始,杀灭率与剂量有关,≥1×MFC。对抗生物膜,d-类似物是最有效的,而l-类似物在大多数菌株中的功效低,甚至是浮游MFC的10倍。稳定性测试表明,d-类似物这种增强的功效可能是由于与l相比,其对蛋白酶降解的抵抗力增强了-模拟。还评估了肽对哺乳动物细胞的毒性。BmKn2和dBmKn2以与MFC相似的水平引起明显的溶血,而Kn2-7和dKn2-7引起的溶血是MFC的4-16倍。在所有测试的白色念珠菌菌株中,dKn2–7对鼠类成纤维细胞的50%抑制浓度(IC 50)大于或等于浮游生物MFC和dKn2–7的生物膜IC 50 s 。这些结果支持了将dKn2-7作为一种新型抗真菌治疗剂进行进一步研究的潜力。

更新日期:2020-06-05
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