Antimicrobial activity of histidine-rich peptides is dependent on acidic conditions
Antimicrobial activity of histidine-rich peptides is dependent on acidic conditions
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DOI：
10.1016/j.bbamem.2007.06.020
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发表时间：
2007-11-01
影响因子：
3.4
通讯作者：
Schmidtchen, Artur
中科院分区：
文献类型：
--
作者：
Kacprzyk, Lukasz;Rydengard, Victoria;Schmidtchen, Artur
由公认的肝素结合Cardin和Wetraub序列Akkara和ARKKAKA的倍数组成的合成肽具有抗菌活性。这些多肽中的赖氨酸和精氨酸被组氨酸取代，在中性pH下完全丧失了它们的抗菌和肝素结合活性。而对革兰氏阴性菌(大肠杆菌、铜绿假单胞菌)、革兰氏阳性菌(枯草芽孢杆菌和金黄色葡萄球菌)以及真菌白色念珠菌的抗菌活性在酸性条件下(pH 5.5)恢复。荧光显微镜和流式细胞仪分析表明，在pH值为5.5时，富含组氨酸的多肽与大肠杆菌和念珠菌的结合显著增强。同样，用于评估膜通透性的荧光研究以及多肽处理的细菌的电子显微镜分析，与多肽对脂质体的影响研究相结合，表明多肽仅在酸性pH下才能诱导膜溶解。富含组氨酸的多肽没有明显的溶血现象。来自人激肽原的富含组氨酸和肝素结合区的多肽和富含组氨酸的糖蛋白的多肽也显示出类似的pH依赖的抗菌活性。结果表明，ART酸性环境的存在是富含组氨酸的抗菌肽活性的重要调节因素。(C)2007 Elsevier B.V.保留所有权利。
Synthetic peptides composed of multiples of the consensus heparin-binding Cardin and Weintraub sequences AKKARA and ARKKAAKA are antimicrobial. Replacement of lysine and arginine by histidine in these peptides completely abrogates their antimicrobial and heparin-binding activities at neutral pH. However, the antibacterial activity against Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) as well as the fungus Candida albicans, was restored at acidic conditions (pH 5.5). Fluorescence microscopy and FACS analysis showed that the binding of the histidine-rich peptides to E. coli and Candida was significantly enhanced at pH 5.5. Likewise, fluorescence studies for assessment of membrane permeation as well as electron microscopy analysis of peptide-treated bacteria, paired with studies of peptide effects on liposomes, demonstrated that the peptides induce membrane lysis only at acidic pH. No discernible hemolysis was noted for the histidine-rich peptides. Similar pH-dependent antimicrobial activities were demonstrated for peptides derived from histidine-rich and heparin-binding regions of human kininogen and histidine-rich glycoprotein. The results demonstrate that the presence of art acidic environment is an important regulator of the activity of histidine-rich antimicrobial peptides. (c) 2007 Elsevier B.V. All rights reserved.