In-Membrane Nanostructuring of Cationic Amphiphiles Affects Their Antimicrobial Efficacy and Cytotoxicity: A Comparison Study between a De Novo Antimicrobial Lipopeptide and Traditional Biocides.
In-Membrane Nanostructuring of Cationic Amphiphiles Affects Their Antimicrobial Efficacy and Cytotoxicity: A Comparison Study between a De Novo Antimicrobial Lipopeptide and Traditional Biocides.
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膜内纳米结构对阳离子两亲体抗菌效果和细胞毒性的影响：一种全新抗菌脂肽与传统杀菌剂的比较研究。
DOI：
10.1021/acs.langmuir.2c00506
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发表时间：
2022-05-31
期刊：
影响因子：
3.9
通讯作者：
Lu, Jian Ren
中科院分区：
文献类型：
--
作者：
Fa, Ke;Liu, Huayang;Gong, Haoning;Zhang, Lin;Liao, Mingrui;Hu, Xuzhi;Ciumac, Daniela;Li, Peixun;Webster, John;Petkov, Jordan;Thomas, Robert K.;Lu, Jian Ren
长期以来，阳离子杀生物剂已被广泛用作用于感染控制和伤口治疗的个人护理和保健产品中的活性成分，但对其细胞毒性和抗微生物抗性存在担忧。设计的脂肽是缓解这些问题的潜在候选物，因为它们对哺乳动物宿主细胞温和并且对病原微生物膜具有高功效。在这项研究中，从头设计的脂肽，CH 3（CH 2）12 CO-Lys-Lys-Gly-Gly-Ile-Ile-NH 2（C14 KKGGII）的抗菌和细胞毒性性能进行了评估，对两个传统的阳离子生物杀灭剂CnTAB（n = 12和14），具有不同的临界聚集浓度（CAC）。C14 KKGGII显示出比两种杀生物剂对细菌和真菌更有效，但对成纤维细胞宿主细胞更温和。生物物理测量模拟微生物和宿主细胞膜的主要特征，获得了脂质单层模型，使用中子反射和小单层囊泡（SUV），使用荧光素泄漏和zeta电位的变化。结果表明，选择性结合阴离子脂质膜的脂肽和膜内纳米结构，这是明显不同的常规CnTAB的共组装。此外，CnTAB结合到模型膜显示出低选择性，其高细胞毒性可归因于膜溶解和化学毒性。这项工作证明了脂肽的优点和它们进一步发展的潜力，走向临床应用。
Cationic biocides have been widely used as active ingredients in personal care and healthcare products for infection control and wound treatment for a long time, but there are concerns over their cytotoxicity and antimicrobial resistance. Designed lipopeptides are potential candidates for alleviating these issues because of their mildness to mammalian host cells and their high efficacy against pathogenic microbial membranes. In this study, antimicrobial and cytotoxic properties of a de novo designed lipopeptide, CH3(CH2)12CO-Lys-Lys-Gly-Gly-Ile-Ile-NH2 (C14KKGGII), were assessed against that of two traditional cationic biocides CnTAB (n = 12 and 14), with different critical aggregation concentrations (CACs). C14KKGGII was shown to be more potent against both bacteria and fungi but milder to fibroblast host cells than the two biocides. Biophysical measurements mimicking the main features of microbial and host cell membranes were obtained for both lipid monolayer models using neutron reflection and small unilamellar vesicles (SUVs) using fluorescein leakage and zeta potential changes. The results revealed selective binding to anionic lipid membranes from the lipopeptide and in-membrane nanostructuring that is distinctly different from the co-assembly of the conventional CnTAB. Furthermore, CnTAB binding to the model membranes showed low selectivity, and its high cytotoxicity could be attributed to both membrane lysis and chemical toxicity. This work demonstrates the advantages of the lipopeptides and their potential for further development toward clinical application.
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影响因子：
3.7
作者：
Inácio ÂS;Mesquita KA;Baptista M;Ramalho-Santos J;Vaz WL;Vieira OV
通讯作者：
Vieira OV
影响因子：
2.2
作者：
Durham, Elizabeth;Dorr, Brent;Woetzel, Nils;Staritzbichler, Rene;Meiler, Jens
通讯作者：
Meiler, Jens
影响因子：
3.4
作者：
Forman, Megan E.;Fletcher, Madison H.;Wuest, William M.
通讯作者：
Wuest, William M.
影响因子：
9.5
作者：
Gong, Haoning;Sani, Marc-Antoine;Lu, Jian Ren
通讯作者：
Lu, Jian Ren
影响因子：
4.9
作者：
Furi, Leonardo;Ciusa, Maria Laura;Oggioni, Marco Rinaldo
通讯作者：
Oggioni, Marco Rinaldo