A Library Approach to Cationic Amphiphilic Polyproline Helices that Target Intracellular Pathogenic Bacteria,ACS Infectious Diseases

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A Library Approach to Cationic Amphiphilic Polyproline Helices that Target Intracellular Pathogenic Bacteria
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2018-07-06 00:00:00 , DOI: 10.1021/acsinfecdis.8b00124
Manish Nepal ₁ , Mohamed F. Mohamed ₂ , Reena Blade ₁ , Hassan E. Eldesouky ₂ , Tiffany N. Anderson ₁ , Mohamed N. Seleem ₂ , Jean Chmielewski ₁

Affiliation

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, and Listeria) residing within macrophages. Furthermore, the selected CAPHs also significantly reduced bacterial infections in an in vivo model of Caenorhabditis elegans, with minimal in vivo toxicity.

中文翻译：

靶向细胞内病原细菌的阳离子两亲性聚脯氨酸螺旋的文库方法

许多致病细菌在哺乳动物细胞内繁殖，因此许多抗菌药物难以获得。在这里，我们提出了一种简便的方法来对称为阳离子两亲性聚脯氨酸螺旋（CAPHs）的抗菌剂的聚焦库进行处理。我们从文库中鉴定出三种CAPH，它们在巨噬细胞中具有出色的细胞渗透性，并且对革兰氏阳性和革兰氏阴性细菌均具有出色的抗菌作用。这些穿透细胞的抗菌CAPH具有特定的亚细胞定位，可将病原菌靶向其细胞内壁ches，这一独特功能可促进成功清除细胞内病原体（沙门氏菌，志贺氏菌和李斯特菌）驻留在巨噬细胞中。此外，在秀丽隐杆线虫的体内模型中，选定的CAPHs还可以显着减少细菌感染，并且体内毒性最小。

更新日期：2018-07-06

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