Majed M Masadeh, Haneen Alshogran, Mohammad Alsaggar, Salsabeel H Sabi, Enaam M Al Momany, Majd M Masadeh, Nasr Alrabadi, Karem H Alzoubi
{"title":"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。","authors":"Majed M Masadeh, Haneen Alshogran, Mohammad Alsaggar, Salsabeel H Sabi, Enaam M Al Momany, Majd M Masadeh, Nasr Alrabadi, Karem H Alzoubi","doi":"10.2174/0113892037291252240528110516","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 (<i>Staphylococcus aureus</i> ATCC 29213, <i>Escherichia coli</i> ATCC 25922) and two resistant (Methicillin-resistant <i>Staphylococcus aureus</i> (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 IC<sub>50</sub> value. Besides the percentage of hemolysis action, the peptide was tested in freshly heparinized blood.</p><p><strong>Results: </strong>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 IC<sub>50</sub> 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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Evaluation of Novel HLM Peptide Activity and Toxicity against Planktonic and Biofilm Bacteria: Comparison to Standard Antibiotics.\",\"authors\":\"Majed M Masadeh, Haneen Alshogran, Mohammad Alsaggar, Salsabeel H Sabi, Enaam M Al Momany, Majd M Masadeh, Nasr Alrabadi, Karem H Alzoubi\",\"doi\":\"10.2174/0113892037291252240528110516\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 (<i>Staphylococcus aureus</i> ATCC 29213, <i>Escherichia coli</i> ATCC 25922) and two resistant (Methicillin-resistant <i>Staphylococcus aureus</i> (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 IC<sub>50</sub> value. Besides the percentage of hemolysis action, the peptide was tested in freshly heparinized blood.</p><p><strong>Results: </strong>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 IC<sub>50</sub> 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.</p><p><strong>Conclusion: </strong>The results indicated that HLM-hybridized peptide displayed a broad-spectrum activity toward different bacterial strains in planktonic and biofilm forms. 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Evaluation of Novel HLM Peptide Activity and Toxicity against Planktonic and Biofilm Bacteria: Comparison to Standard Antibiotics.
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.
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.
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