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设计的阳离子抗菌肽的协同潜力及作用机制评估

Evaluation of the synergistic potential and mechanisms of action for designed cationic antimicrobial peptides.

作者信息

Karapetian Margarita, Alimbarashvili Evgenia, Vishnepolsky Boris, Gabrielian Andrei, Rosenthal Alex, Hurt Darrell E, Tartakovsky Michael, Mchedlishvili Mariam, Arsenadze Davit, Pirtskhalava Malak, Zaalishvili Giorgi

机构信息

Laboratory of Chromatin Biology, Institute of Cellular and Molecular Biology, Agricultural University of Georgia, 240 David Aghmashenebeli Alley, 0159, Tbilisi, Georgia.

Ivane Beritashvili Center of Experimental Biomedicine, 0160, Tbilisi, Georgia.

出版信息

Heliyon. 2024 Mar 13;10(6):e27852. doi: 10.1016/j.heliyon.2024.e27852. eCollection 2024 Mar 30.

DOI:10.1016/j.heliyon.2024.e27852
PMID:38560672
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10979160/
Abstract

Antimicrobial peptides (AMPs) have emerged as promising candidates in combating antimicrobial resistance - a growing issue in healthcare. However, to develop AMPs into effective therapeutics, a thorough analysis and extensive investigations are essential. In this study, we employed an approach to design cationic AMPs , followed by their experimental testing. The antibacterial potential of designed cationic AMPs, along with their synergistic properties in combination with conventional antibiotics was examined. Furthermore, the effects of bacterial inoculum density and metabolic state on the antibacterial activity of AMPs were evaluated. Finally, the impact of several potent AMPs on cell envelope and genomic DNA integrity was determined. Collectively, this comprehensive analysis provides insights into the unique characteristics of cationic AMPs.

摘要

抗菌肽（AMPs）已成为对抗抗菌药物耐药性这一医疗保健领域日益严重问题的有前景的候选物。然而，要将抗菌肽开发成有效的治疗药物，进行全面分析和广泛研究至关重要。在本研究中，我们采用一种方法设计阳离子抗菌肽，随后进行实验测试。研究了设计的阳离子抗菌肽的抗菌潜力，以及它们与传统抗生素联合使用时的协同特性。此外，还评估了细菌接种密度和代谢状态对抗菌肽抗菌活性的影响。最后，确定了几种强效抗菌肽对细胞包膜和基因组DNA完整性的影响。总体而言，这一全面分析为阳离子抗菌肽的独特特性提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db02/10979160/07b671489c27/mmcfigs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db02/10979160/835d282cbee9/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db02/10979160/08c547d67092/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db02/10979160/ac8d940c9fdd/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db02/10979160/0bc170334227/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db02/10979160/1e074485de34/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db02/10979160/7f2373e4e9ad/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db02/10979160/07b671489c27/mmcfigs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db02/10979160/835d282cbee9/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db02/10979160/08c547d67092/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db02/10979160/ac8d940c9fdd/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db02/10979160/0bc170334227/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db02/10979160/1e074485de34/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db02/10979160/7f2373e4e9ad/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db02/10979160/07b671489c27/mmcfigs2.jpg

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本文引用的文献

1
Antimicrobial activity of cationic antimicrobial peptides against stationary phase bacteria.阳离子抗菌肽对稳定期细菌的抗菌活性。
Front Microbiol. 2022 Oct 25;13:1029084. doi: 10.3389/fmicb.2022.1029084. eCollection 2022.
2
Antimicrobial Peptides-Mechanisms of Action, Antimicrobial Effects and Clinical Applications.抗菌肽——作用机制、抗菌效果及临床应用
Antibiotics (Basel). 2022 Oct 16;11(10):1417. doi: 10.3390/antibiotics11101417.
3
Comparative analysis of machine learning algorithms on the microbial strain-specific AMP prediction.
机器学习算法在微生物菌株特异性 AMP 预测上的比较分析。
Brief Bioinform. 2022 Jul 18;23(4). doi: 10.1093/bib/bbac233.
4
Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis.2019 年全球细菌对抗菌药物耐药性的负担：系统分析。
Lancet. 2022 Feb 12;399(10325):629-655. doi: 10.1016/S0140-6736(21)02724-0. Epub 2022 Jan 19.
5
Developing Antimicrobial Synergy With AMPs.利用抗菌肽开发抗菌协同作用。
Front Med Technol. 2021 Mar 12;3:640981. doi: 10.3389/fmedt.2021.640981. eCollection 2021.
6
Structure and Formation Mechanism of Antimicrobial Peptides Temporin B- and L-Induced Tubular Membrane Protrusion.抗菌肽 Temporin B- 和 L 诱导管状膜突起的结构和形成机制。
Int J Mol Sci. 2021 Oct 13;22(20):11015. doi: 10.3390/ijms222011015.
7
Antibiotic Potentiation in Multidrug-Resistant Gram-Negative Pathogenic Bacteria by a Synthetic Peptidomimetic.合成肽类似物增强多重耐药革兰氏阴性病原菌中的抗生素作用。
ACS Infect Dis. 2021 Aug 13;7(8):2152-2163. doi: 10.1021/acsinfecdis.1c00147. Epub 2021 Jul 6.
8
Physicochemical Features and Peculiarities of Interaction of AMP with the Membrane.AMP与膜相互作用的物理化学特征及特性
Pharmaceuticals (Basel). 2021 May 17;14(5):471. doi: 10.3390/ph14050471.
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The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions.抗菌肽的多面性：当前的合成化学方法和未来方向。
Chem Soc Rev. 2021 Jul 5;50(13):7820-7880. doi: 10.1039/d0cs00729c.
10
Inoculum effect of antimicrobial peptides.抗菌肽的接种效应。
Proc Natl Acad Sci U S A. 2021 May 25;118(21). doi: 10.1073/pnas.2014364118.