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一种通过插入细胞膜选择性杀死革兰氏阳性菌的紫红素-肽衍生物。

A purpurin-peptide derivative for selective killing of Gram-positive bacteria via insertion into cell membrane.

作者信息

Zhou Jin, Qi Guo-Bin, Wang Hao

机构信息

CAS Center for Excellence in Nanoscience, Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, China.

出版信息

J Mater Chem B. 2016 Jul 28;4(28):4855-4861. doi: 10.1039/c6tb00406g. Epub 2016 Jun 28.

DOI:10.1039/c6tb00406g
PMID:32263144
Abstract

Pathogenic bacteria can cause significant morbidity and become a critical public healthcare problem. To date, effective identification and killing of bacteria remains a major challenge in bacterial infections. Although numerous materials have been designed for bacteria identification, few materials can discriminate different bacteria effectively. In this work, we designed a new polyarginine chlorophyll derivative (PA7) that can identify different bacteria successfully. PA7 was composed of a cationic hydrophilic chain and a hydrophobic purpurin-18 core and had variable binding capabilities towards different bacteria based on their surface components and structure. We observed that the PA7 molecule preferentially bound to Gram-positive bacteria (i.e., S. aureus) over Gram-negative bacteria (i.e., E. coli) through CLSM imaging. Furthermore, ζ potential experiments indicated that the binding ability of PA7 to Gram-negative (E. coli) was more susceptible to the ionic strength. Given the fact that the two kinds of bacteria possess different cell envelope components, we speculated that the binding of PA7 to S. aureus was dominated by electrostatic and hydrophobic interactions, and only electrostatic interactions for E.coli. Moreover, PA7 could be used as a good photoacoustic contrast agent. PA7 could discriminate Gram-positive bacteria and Gram-negative bacteria via photoacoustic imaging in a buffer solution with variable ionic strengths. Effective killing of bacteria was another motivation of the molecular design. PA7, as a potential photosensitizer, exhibited a much higher photodynamic antibacterial activity to S. aureus.

摘要

致病细菌可导致严重发病,并成为一个关键的公共卫生保健问题。迄今为止,有效识别和杀灭细菌仍然是细菌感染领域的一项重大挑战。尽管已经设计了许多用于细菌识别的材料,但很少有材料能够有效地区分不同的细菌。在这项工作中,我们设计了一种新型聚精氨酸叶绿素衍生物(PA7),它能够成功识别不同的细菌。PA7由阳离子亲水链和疏水的紫红素-18核心组成,基于不同细菌的表面成分和结构,它对不同细菌具有不同的结合能力。通过共聚焦激光扫描显微镜(CLSM)成像,我们观察到PA7分子优先结合革兰氏阳性菌(即金黄色葡萄球菌)而非革兰氏阴性菌(即大肠杆菌)。此外,ζ电位实验表明,PA7与革兰氏阴性菌(大肠杆菌)的结合能力更容易受到离子强度的影响。鉴于这两种细菌具有不同的细胞壁成分,我们推测PA7与金黄色葡萄球菌的结合主要由静电和疏水相互作用主导,而与大肠杆菌的结合仅涉及静电相互作用。此外,PA7可作为一种良好的光声造影剂。在具有不同离子强度的缓冲溶液中,PA7能够通过光声成像区分革兰氏阳性菌和革兰氏阴性菌。有效杀灭细菌是分子设计的另一个动机。PA7作为一种潜在的光敏剂,对金黄色葡萄球菌表现出更高的光动力抗菌活性。

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