具有高效阳性菌抗菌活性的合成多肽聚合物研究

Synthetic Peptidyl Polymer Displaying Potent Activity Against Gram Positive Bacteria

合成了具有抗菌活性的β-氨基酸聚合物,采用核磁共振和凝胶渗透色谱表征聚合物的数均分子量,通过最低抑菌浓度实验测试了β-氨基酸聚合物对多种革兰氏阳性菌(包括多株耐药菌)的抗菌活性,并开展了可能的耐药性研究。通过细胞膜去极化实验和扫描电子显微镜探究了抗菌聚合物对革兰氏阳性菌,尤其是对耐甲氧西林金黄色葡萄球菌的抗菌机理。结果表明,β-氨基酸聚合物通过作用于细菌的细胞膜杀死革兰氏阳性菌从而获得高效的抗菌活性,其对枯草芽孢杆菌的抗菌活性最好,最低抑菌浓度为3.13μg/mL。金黄色葡萄球菌对β-氨基酸聚合物不产生耐药性,但在相同条件下测试的对照抗生素诺氟沙星的最低抑菌浓度增加了124倍,表明细菌对抗生素很快产生了耐药性。

An antimicrobial poly-β-peptide(β-amino acid polymer)was synthesized and characterized by nuclear magnetic resonance and gel permeation chromatography to give the number-average molecular weight of the polymer.The antibacterial activity of this poly-β-peptide against Gram positive bacteria,including multiple drug-resistant strains,was evaluated by its minimum inhibitory concentration(MIC).The MIC test showed that this poly-β-peptide had potent antibacterial activity(MIC value in the range of 3.13-12.5μg/mL)against multiple strains of Gram positive bacteria,and it demonstrated the best activity toward B.subtilis with a MIC at 3.13μg/mL.Investigation on possible antimicrobial resistance after repeated use of this antimicrobial poly-β-peptide indicated that S.aureus displayed no resistance to this poly-β-peptide.However,the MIC of norfloxacin hydrochloride(the antibiotic control)increased 124 folds in the same test,which indicated that S.aureus developed strong resistance easily against this antibiotic.The antibacterial mechanism of this poly-β-peptide against Gram-positive bacteria,especially methicillin-resistant S.aureus(MRSA),was also investigated using cell membrane depolarization assay and scanning electron microscopy.Results implied that this poly-β-peptide interacted with bacterial cell membrane and killed Gram positive bacteria by disrupting the cell membrane.