Evaluation of Novel HLM Peptide Activity and Toxicity against Planktonic and Biofilm Bacteria: Comparison to Standard Antibiotics.

IF 1.9 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current protein & peptide science Pub Date : 2024-01-01 DOI:10.2174/0113892037291252240528110516

Majed M Masadeh, Haneen Alshogran, Mohammad Alsaggar, Salsabeel H Sabi, Enaam M Al Momany, Majd M Masadeh, Nasr Alrabadi, Karem H Alzoubi

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引用次数: 0

Abstract

Background: Antibiotic resistance is one of the main concerns of public health, and the whole world is trying to overcome such a challenge by finding novel therapeutic modalities and approaches. This study has applied the sequence hybridization approach to the original sequence of two cathelicidin natural parent peptides (BMAP-28 and LL-37) to design a novel HLM peptide with broad antimicrobial activity.

Methods: The physicochemical characteristics of the newly designed peptide were determined. As well, the new peptide's antimicrobial activity (Minimum Inhibitory Concentration (MIC), Minimum Bacterial Eradication Concentration (MBEC), and antibiofilm activity) was tested on two control (Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922) and two resistant (Methicillin-resistant Staphylococcus aureus (MRSA) ATCC BAA41, New Delhi metallo-beta- lactamase-1 Escherichia coli ATCC BAA-2452) bacterial strains. Furthermore, synergistic studies have been applied to HLM-hybridized peptides with five conventional antibiotics by checkerboard assays. Also, the toxicity of HLM-hybridized peptide was studied on Vero cell lines to obtain the IC₅₀ value. Besides the percentage of hemolysis action, the peptide was tested in freshly heparinized blood.

Results: The MIC values for the HLM peptide were obtained as 20, 10, 20, and 20 μM, respectively. Also, the results showed no hemolysis action, with low to slightly moderate toxicity action against mammalian cells, with an IC₅₀ value of 10.06. The Biomatik corporate labs, where HLM was manufactured, determined the stability results of the product by Mass Spectrophotometry (MS) and High-performance Liquid Chromatography (HPLC) methods. The HLM-hybridized peptide exhibited a range of synergistic to additive antimicrobial activities upon combination with five commercially available different antibiotics. It has demonstrated the biofilm-killing effects in the same concentration required to eradicate the control strains.

Conclusion: The results indicated that HLM-hybridized peptide displayed a broad-spectrum activity toward different bacterial strains in planktonic and biofilm forms. It showed synergistic or additive antimicrobial activity upon combining with commercially available different antibiotics.

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评估新型 HLM 肽对浮游细菌和生物膜细菌的活性和毒性：与标准抗生素的比较。

背景：抗生素耐药性是公共卫生的主要问题之一，全世界都在试图通过寻找新的治疗模式和方法来克服这一挑战。本研究采用序列杂交的方法，对两种猫肝素天然母肽（BMAP-28 和 LL-37）的原始序列进行杂交，设计出一种具有广泛抗菌活性的新型 HLM 肽：方法：测定了新设计多肽的理化特性。方法：测定了新设计多肽的理化特性，并在两个对照组（金黄色葡萄球菌 ATCC 29213、大肠埃希菌 ATCC 2213、大肠杆菌 ATCC 2213）上测试了新多肽的抗菌活性[最低抑菌浓度（MIC）、最低除菌浓度（MBEC）和抗生物膜活性]、金黄色葡萄球菌 ATCC 29213、大肠埃希菌 ATCC 25922）和两种耐药菌株[耐甲氧西林金黄色葡萄球菌（MRSA）ATCC BAA41、新德里金属-β-内酰胺酶-1 型大肠埃希菌 ATCC BAA-2452]进行了测试。此外，还通过棋盘试验对 HLM 杂交肽与五种常规抗生素的协同作用进行了研究。此外，还研究了 HLM 杂交肽对 Vero 细胞系的毒性，以获得 IC50 值。除了溶血作用的百分比外，该肽还在新鲜肝素化血液中进行了测试：结果：HLM 肽的 MIC 值分别为 20、10、20 和 20 μM。此外，研究结果表明，HLM 肽对哺乳动物细胞无溶血作用，毒性为低至中等，IC50 值为 10.06。生产 HLM 的 Biomatik 公司实验室通过质谱光度法（MS）和高效液相色谱法（HPLC）测定了产品的稳定性。HLM杂化肽与五种市售不同抗生素结合后，表现出一系列协同和相加的抗菌活性。结论：结果表明，HLM-杂交肽与五种市售不同抗生素的组合具有协同和相加的抗菌活性：结果表明，HLM-杂化肽对浮游和生物膜形态的不同细菌菌株具有广谱活性。它与市售的不同抗生素结合后，显示出协同或相加的抗菌活性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current protein & peptide science 生物-生化与分子生物学

CiteScore

5.20

自引率

0.00%

发文量

审稿时长

6 months

期刊介绍： Current Protein & Peptide Science publishes full-length/mini review articles on specific aspects involving proteins, peptides, and interactions between the enzymes, the binding interactions of hormones and their receptors; the properties of transcription factors and other molecules that regulate gene expression; the reactions leading to the immune response; the process of signal transduction; the structure and function of proteins involved in the cytoskeleton and molecular motors; the properties of membrane channels and transporters; and the generation and storage of metabolic energy. In addition, reviews of experimental studies of protein folding and design are given special emphasis. Manuscripts submitted to Current Protein and Peptide Science should cover a field by discussing research from the leading laboratories in a field and should pose questions for future studies. Original papers, research articles and letter articles/short communications are not considered for publication in Current Protein & Peptide Science.