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抗囊性纤维化患者多药耐药生物膜的抗菌肽。

Antimicrobial Peptides against Multidrug-Resistant Biofilm from Cystic Fibrosis Patients.

机构信息

Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.

Pediatric Pulmonary Institute and National CF Center, Edmond and Lilly Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan 52621, Israel.

出版信息

J Med Chem. 2022 Jul 14;65(13):9050-9062. doi: 10.1021/acs.jmedchem.2c00270. Epub 2022 Jun 27.

Abstract

Lung infection is the leading cause of morbidity and mortality in cystic fibrosis (CF) patients and is mainly dominated by . Treatment of CF-associated lung infections is problematic because the drugs are vulnerable to multidrug-resistant pathogens, many of which are major biofilm producers like . Antimicrobial peptides (AMPs) are essential components in all life forms and exhibit antimicrobial activity. Here we investigated a series of AMPs (d,l-KL), each composed of six lysines and nine leucines but differing in their sequence composed of l- and d-amino acids. The d,l-KL peptides showed antimicrobial and antibiofilm activities against from CF patients. Furthermore, the data revealed that the d,l-KL peptides are stable and resistant to degradation by CF sputum proteases and maintain their activity in a CF sputum environment. Additionally, the d,l-KL peptides do not induce bacterial resistance. Overall, these findings should assist in the future development of alternative treatments against resistant bacterial biofilms.

摘要

肺部感染是囊性纤维化 (CF) 患者发病率和死亡率的主要原因,主要由 引起。CF 相关肺部感染的治疗存在问题,因为这些药物容易受到多种耐药病原体的影响,其中许多是主要的生物膜生产者,如 。抗菌肽 (AMPs) 是所有生命形式的重要组成部分,具有抗菌活性。在这里,我们研究了一系列 AMPs (d,l-KL),它们均由六个赖氨酸和九个亮氨酸组成,但在由 l-和 d-氨基酸组成的序列上有所不同。d,l-KL 肽对来自 CF 患者的 表现出抗菌和抗生物膜活性。此外,数据显示 d,l-KL 肽稳定且不易被 CF 痰液蛋白酶降解,并在 CF 痰液环境中保持其活性。此外,d,l-KL 肽不会诱导细菌耐药性。总的来说,这些发现应该有助于未来开发针对耐药细菌生物膜的替代治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d2f/9289885/03b9116763d2/jm2c00270_0001.jpg

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