当前位置: X-MOL 学术BBA Gen. Subj. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Differential interactions of the antimicrobial peptide, RQ18, with phospholipids and cholesterol modulate its selectivity for microorganism membranes
Biochimica et Biophysica Acta (BBA) - General Subjects ( IF 3 ) Pub Date : 2021-05-27 , DOI: 10.1016/j.bbagen.2021.129937
Claudiane V Almeida 1 , Caio F R de Oliveira 2 , Edson L Dos Santos 3 , Helder F Dos Santos 3 , Edson C Júnior 4 , Reinaldo Marchetto 4 , Leticia A da Cruz 5 , Alda Maria T Ferreira 5 , Valdirene M Gomes 6 , Gabriel B Taveira 6 , Bruna O Costa 7 , Octávio L Franco 8 , Marlon H Cardoso 8 , Maria Lígia R Macedo 1
Affiliation  

Background

Antimicrobial peptides (AMPs) are molecules with potential application for the treatment of microorganism infections. We, herein, describe the structure, activity, and mechanism of action of RQ18, an α-helical AMP that displays antimicrobial activity against Gram-positive and Gram-negative bacteria, and yeasts from the Candida genus.

Methods

A physicochemical-guided design assisted by computer tools was used to obtain our lead peptide candidate, named RQ18. This peptide was assayed against Gram-positive and Gram-negative bacteria, yeasts, and mammalian cells to determine its selectivity index. The secondary structure and the mechanism of action of RQ18 were investigated using circular dichroism, large unilamellar vesicles, and molecular dynamic simulations.

Results

RQ18 was not cytotoxic to human lung fibroblasts, peripheral blood mononuclear cells, red blood cells, or Vero cells at MIC values, exhibiting a high selectivity index. Circular dichroism analysis and molecular dynamic simulations revealed that RQ18 presents varying structural profiles in aqueous solution, TFE/water mixtures, SDS micelles, and lipid bilayers. The peptide was virtually unable to release carboxyfluorescein from large unilamellar vesicles composed of POPC/cholesterol, model that mimics the eukaryotic membrane, indicating that vesicles' net charges and the presence of cholesterol may be related with RQ18 selectivity for bacterial and fungal cell surfaces.

Conclusions

RQ18 was characterized as a membrane-active peptide with dual antibacterial and antifungal activities, without compromising mammalian cells viability, thus reinforcing its therapeutic application.

General significance

These results provide further insight into the complex process of AMPs interaction with biological membranes, in special with systems that mimic prokaryotic and eukaryotic cell surfaces.



中文翻译:

抗菌肽 RQ18 与磷脂和胆固醇的不同相互作用调节其对微生物膜的选择性

背景

抗微生物肽 (AMP) 是具有治疗微生物感染潜在应用的分子。我们在此描述了 RQ18 的结构、活性和作用机制,RQ18 是一种 α-螺旋 AMP,对革兰氏阳性菌和革兰氏阴性菌以及念珠菌属的酵母菌具有抗菌活性。

方法

计算机工具辅助的物理化学引导设计用于获得我们的先导肽候选物,命名为 RQ18。该肽针对革兰氏阳性和革兰氏阴性细菌、酵母和哺乳动物细胞进行了测定,以确定其选择性指数。使用圆二色性、大单层囊泡和分子动力学模拟研究了 RQ18 的二级结构和作用机制。

结果

RQ18 在 MIC 值下对人肺成纤维细胞、外周血单核细胞、红细胞或 Vero 细胞没有细胞毒性,表现出高选择性指数。圆二色性分析和分子动力学模拟表明,RQ18 在水溶液、TFE/水混合物、SDS 胶束和脂质双层中呈现出不同的结构特征。该肽实际上无法从由 POPC/胆固醇组成的大单层囊泡中释放羧基荧光素,模拟真核细胞膜的模型,表明囊泡的净电荷和胆固醇的存在可能与 RQ18 对细菌和真菌细胞表面的选择性有关。

结论

RQ18 被表征为具有双重抗菌和抗真菌活性的膜活性肽,不会影响哺乳动物细胞的活力,从而加强了其治疗应用。

一般意义

这些结果提供了对 AMP 与生物膜相互作用的复杂过程的进一步了解,特别是模拟原核和真核细胞表面的系统。

更新日期:2021-06-11
down
wechat
bug