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开发具有增强稳定性和低毒性的抗多药耐药菌杀菌肽。

Development of Bactericidal Peptides against Multidrug-Resistant with Enhanced Stability and Low Toxicity.

机构信息

Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, 23-10 Dahuen Road., Ilan 262, Taiwan.

Institute of Fisheries Science, National Taiwan University, 1 Roosevelt Road, Section 4, Taipei 112, Taiwan.

出版信息

Int J Mol Sci. 2022 Feb 16;23(4):2191. doi: 10.3390/ijms23042191.

Abstract

Pathogenic superbugs are the root cause of untreatable complex infections with limited or no treatment options. These infections are becoming more common as clinical antibiotics have lost their effectiveness over time. Therefore, the development of novel antibacterial agents is urgently needed to counter these microbes. Antimicrobial peptides (AMPs) are a viable treatment option due to their bactericidal potency against multiple microbial classes. AMPs are naturally selected physiological microbicidal agents that are found in all forms of organisms. In the present study, we developed two tilapia piscidin 2 (TP2)-based AMPs for antimicrobial application. Unlike the parent peptide, the redesigned peptides showed significant antimicrobial activity against multidrug-resistant bacterial species. These peptides also showed minimal cytotoxicity. In addition, they were significantly active in the presence of physiological salts, 50% human serum and elevated temperature. The designed peptides also showed synergistic activity when combined with clinical antibiotics. The current approach demonstrates a fruitful strategy for developing potential AMPs for antimicrobial application. Such AMPs have potential for progression to further trials and drug development investigations.

摘要

致病超级细菌是导致治疗选择有限或无法治疗的复杂感染的根本原因。随着临床抗生素随着时间的推移失去功效,这些感染变得越来越普遍。因此,迫切需要开发新型抗菌剂来对抗这些微生物。抗菌肽 (AMP) 是一种可行的治疗选择,因为它们对多种微生物类别的杀菌能力。AMP 是天然选择的生理杀菌剂,存在于所有生物体形式中。在本研究中,我们开发了两种基于罗非鱼抗菌肽 2 (TP2) 的 AMP 用于抗菌应用。与亲本肽不同,重新设计的肽对多种耐多药细菌具有显著的抗菌活性。这些肽也表现出最小的细胞毒性。此外,它们在存在生理盐、50%人血清和高温时仍具有显著的活性。设计的肽与临床抗生素联合使用时也表现出协同活性。目前的方法为开发用于抗菌应用的潜在 AMP 提供了一条富有成效的策略。这些 AMP 有可能进一步进行试验和药物开发研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b179/8875074/b209d68ab4a0/ijms-23-02191-g001.jpg

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