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开发抗菌肽作为对抗抗生素耐药性感染的一种有前景的治疗方法。

Developing antibacterial peptides as a promising therapy for combating antibiotic-resistant infections.

作者信息

Darwish Rula M, Salama Ali H

机构信息

Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, the University of Jordan, Amman, 11942, Jordan.

Department of Pharmacy, Faculty of Pharmacy, Middle East University, Amman, 11831, Jordan.

出版信息

Vet World. 2024 Jun;17(6):1259-1264. doi: 10.14202/vetworld.2024.1259-1264. Epub 2024 Jun 8.

Abstract

BACKGROUND AND AIM

Antibiotic-resistant poses a serious health threat. This study aimed to investigate the antibacterial activity of peptide KW-23 against drug-resistant and its potential for enhancing the efficacy of conventional antibiotics.

MATERIALS AND METHODS

KW-23 was synthesized from nine amino acids, specifically three tryptophans and three lysines. The purity of the substance was analyzed using reverse-phase high-performance liquid chromatography. The peptide was identified through mass spectrometry using electrospray ionization. The minimum inhibitory concentration (MIC) values of KW-23 in combination with conventional antibiotics against control and multidrug-resistant were determined utilizing broth microdilution. The erythrocyte hemolytic assay was used to measure toxicity. The KW-23 effect was analyzed using the time-kill curve.

RESULTS

The peptide exhibited strong antibacterial activity against control and multidrug-resistant strains of , with MICs of 4.5 μg/mL and 20 μg/mL, respectively. At higher concentration of 100 μg/mL, KW-23 exhibited a low hemolytic impact, causing no more than 3% damage to red blood. The cytotoxicity assay demonstrates KW-23's safety, while the time-kill curve highlights its rapid and sustained antibacterial activity. The combination of KW-23 and gentamicin exhibited synergistic activity against both susceptible and resistant , with fractional inhibitory concentration index values of 0.07 and 0.27, respectively.

CONCLUSION

The KW-23 synthesized in the laboratory significantly combats antibiotic-resistant . Due to its strong antibacterial properties and low toxicity to cells, KW-23 is a promising alternative to traditional antibiotics in combating multidrug-resistant bacteria.

摘要

背景与目的

抗生素耐药性对健康构成严重威胁。本研究旨在探究肽KW - 23对耐药菌的抗菌活性及其增强传统抗生素疗效的潜力。

材料与方法

KW - 23由九个氨基酸合成,具体为三个色氨酸和三个赖氨酸。使用反相高效液相色谱分析该物质的纯度。通过电喷雾电离质谱法鉴定该肽。利用肉汤微量稀释法测定KW - 23与传统抗生素联合对对照菌和多重耐药菌的最低抑菌浓度(MIC)值。采用红细胞溶血试验测量毒性。使用时间 - 杀菌曲线分析KW - 23的作用效果。

结果

该肽对对照菌和多重耐药菌均表现出较强的抗菌活性,MIC分别为4.5μg/mL和20μg/mL。在100μg/mL的较高浓度下,KW - 23对红细胞的溶血影响较低,对红细胞的损伤不超过3%。细胞毒性试验证明了KW - 23的安全性,而时间 - 杀菌曲线突出了其快速且持续的抗菌活性。KW - 23与庆大霉素联合对敏感菌和耐药菌均表现出协同活性,部分抑菌浓度指数值分别为0.07和0.27。

结论

实验室合成的KW - 23能有效对抗抗生素耐药菌。由于其强大的抗菌特性和对细胞的低毒性,KW - 23在对抗多重耐药菌方面是传统抗生素的一个有前景的替代品。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d36/11283607/ac33f1ec4c2b/Vetworld-17-1259-g001.jpg

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