Fusion of Lysostaphin to an Albumin Binding Domain Prolongs Its Half-Life and Bactericidal Activity in the Systemic Circulation
| العنوان: | Fusion of Lysostaphin to an Albumin Binding Domain Prolongs Its Half-Life and Bactericidal Activity in the Systemic Circulation |
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| المؤلفون: | N V Lavrova, Anna S. Karyagina, Maria S. Generalova, Vladimir G. Lunin, N. B. Polyakov, A. V. Grishin, Lyubov’ A. Soboleva, Nikita V. Shestak, A. M. Lyashchuk, N V Strukova, Z. M. Galushkina, Anna V. Ryazanova, I. S. Boksha, Liubov I. Popova |
| المصدر: | Molecules Volume 24 Issue 16 Molecules, Vol 24, Iss 16, p 2892 (2019) |
| بيانات النشر: | MDPI AG, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Staphylococcus aureus, antibiotic resistance, Recombinant Fusion Proteins, Lysin, Serum albumin, Pharmaceutical Science, Pharmacology, Article, Analytical Chemistry, lcsh:QD241-441, 03 medical and health sciences, lcsh:Organic chemistry, Bacterial Proteins, Drug Discovery, pharmacodynamics, Animals, lysin, Rats, Wistar, Physical and Theoretical Chemistry, Serum Albumin, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, Lysostaphin, Chemistry, Organic Chemistry, Albumin, Fusion protein, albumin-binding domain, Rats, Chemistry (miscellaneous), endolysin, biology.protein, PEGylation, Molecular Medicine, Female, lysostaphin, Antibacterial activity, pharmacokinetics, Binding domain |
| الوصف: | Antibacterial lysins are promising proteins that are active against both antibiotic-susceptible and antibiotic-resistant bacterial strains. However, a major limitation of antibacterial lysins is their fast elimination from systemic circulation. PEGylation increases the plasma half-life of lysins but renders them inactive. Here we report the construction of a fusion protein of lysostaphin, a potent anti-staphylococcal lysin, and an albumin-binding domain from streptococcal protein G. The resulting fusion protein was less active than the parent enzyme lysostaphin, but it still retained significant antibacterial activity even when bound to serum albumin. The terminal half-life of the fusion protein in rats was five-fold greater than that of lysostaphin (7.4 vs. 1.5 h), and the area under the curve increased more than 115 times. Most importantly, this increase in systemic circulation time compensated for the decrease in activity. The plasma from rats that received an injection of the fusion protein retained bactericidal activity for up to 7 h, while plasma from rats that received plain lysostaphin lacked any detectable activity after 4 h. To the best of our knowledge, this is the first report of an antibacterial lysin with both improved pharmacokinetic parameters and prolonged bactericidal activity in the systemic circulation. |
| وصف الملف: | application/pdf |
| تدمد: | 1420-3049 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b17dea016fd67218d04878e01e0e2aea https://doi.org/10.3390/molecules24162892 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....b17dea016fd67218d04878e01e0e2aea |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14203049 |
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