A Library Approach to Cationic Amphiphilic Polyproline Helices that Target Intracellular Pathogenic Bacteria
A Library Approach to Cationic Amphiphilic Polyproline Helices that Target Intracellular Pathogenic Bacteria
复制标题
针对细胞内致病细菌的阳离子两亲性聚脯氨酸螺旋的文库方法
DOI：
10.1021/acsinfecdis.8b00124
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发表时间：
2018
影响因子：
5.3
通讯作者：
Chmielewski, Jean
中科院分区：
文献类型：
--
作者：
Nepal, Manish;Mohamed, Mohamed F.;Blade, Reena;Eldesouky, Hassan E.;N. Anderson, Tiffany;Seleem, Mohamed N.;Chmielewski, Jean
许多致病菌在哺乳动物细胞内繁殖，因此许多抗菌药物无法获得。在这里，我们提出了一种简便的方法来获得抗菌剂的聚集库，称为阳离子两亲性多聚脯氨酸螺旋(CAPHs)。我们从文库中鉴定出三种CAPHs，它们在巨噬细胞内具有良好的细胞渗透性，对革兰氏阳性菌和革兰氏阴性菌都有良好的抗菌作用。这些穿透细胞的抗菌CAPH具有特定的亚细胞定位，允许在其细胞内利基定位致病菌，这是一个独特的功能，促进了驻留在巨噬细胞内的细胞内病原体(沙门氏菌、志贺氏菌和李斯特菌)的成功清除。此外，所选择的CAPHs还显著减少了秀丽隐杆线虫活体模型中的细菌感染，具有最低的活体毒性。
A number of pathogenic bacteria reproduce inside mammalian cells and are thus inaccessible to many antimicrobial drugs. Herein, we present a facile method to a focused library of antibacterial agents known as cationic amphiphilic polyproline helices (CAPHs). We identified three CAPHs from the library with superior cell penetration within macrophages and excellent antibacterial action against both Gram-positive and Gram-negative bacteria. These cell-penetrating antibacterial CAPHs have specific subcellular localizations that allow for targeting of pathogenic bacteria at their intracellular niches, a unique feature that promotes the successful clearance of intracellular pathogens (Salmonella,Shigella, andListeria) residing within macrophages. Furthermore, the selected CAPHs also significantly reduced bacterial infections in anin vivomodel ofCaenorhabditis elegans, with minimalin vivotoxicity.