Lee Dong Gun, Park Yoonkyung, Kim Pyoung Il, Jeong Hye Gwang, Woo Eun-Rhan, Hahm Kyung-Soo
Research Center for Proteineous Materials, Chosun University, 375 Seosuk-Dong, Dong-Ku, Kwangju 501-759, South Korea.
Biochem Biophys Res Commun. 2002 Oct 4;297(4):885-9.
A 20-residue hybrid peptide (HP (2-9)-MA (1-12): HP-MA), incorporating 2-9 residues of Helicobacter pyroli ribosomal protein L1 (HP) and 1-12 residues of magainin 2 (MA), has more potent antibacterial activity than parent peptide HP (2-20) and magainin 2. In this study, the antifungal activity and its mechanism of HP-MA were investigated. HP-MA displayed a strong antifungal activity in an energy-dependent manner. To elucidate the antifungal mechanism(s) of HP-MA, FACScan analysis and the change in membrane dynamics using 1,6-diphenyl-1,3,5-hexatriene (DPH) as a membrane probe of Candida albicans were examined. The results indicated that the HP-MA exerts its antifungal effect by acting on the plasma membrane. Furthermore, the peptide induced remarkable morphological change when tested for membrane disrupting activity using liposomes (PC/Cholesterol; 10:1, w/w). In C. albicans, dimorphism plays a crucial role in pathogenesis but HP-MA could disrupt the mycelial forms and exert its antifungal effect on the blastoconidia in 20% fetal bovine serum.
一种包含20个氨基酸残基的杂合肽(HP(2 - 9)-MA(1 - 12):HP - MA),融合了幽门螺杆菌核糖体蛋白L1的2 - 9个残基(HP)和蛙皮素2的1 - 12个残基(MA),其抗菌活性比亲本肽HP(2 - 20)和蛙皮素2更强。在本研究中,对HP - MA的抗真菌活性及其机制进行了研究。HP - MA以能量依赖的方式表现出强大的抗真菌活性。为了阐明HP - MA的抗真菌机制,采用FACScan分析以及使用1,6 - 二苯基 - 1,3,5 - 己三烯(DPH)作为白色念珠菌膜探针检测膜动力学变化。结果表明,HP - MA通过作用于质膜发挥其抗真菌作用。此外,当使用脂质体(PC/胆固醇;10:1,w/w)检测膜破坏活性时,该肽诱导了显著的形态变化。在白色念珠菌中,二态性在发病机制中起关键作用,但HP - MA可以破坏菌丝形态并对20%胎牛血清中的芽生孢子发挥抗真菌作用。