Chimeric Beta-Defensin Analogs, Including the Novel 3NI Analog, Display Salt-Resistant Antimicrobial Activity and Lack Toxicity in Human Epithelial Cell Lines
| Autor: | Olga Scudiero, Francesco Salvatore, Aurora Daniele, Carlo Pedone, Jean-Jacques Cassiman, Stefania Galdiero, Marco Cantisani, Ersilia Nigro, Luigi Del Vecchio, Irene Colavita, Rosa Di Noto, Massimiliano Galdiero |
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| Přispěvatelé: | Scudiero, O, Galdiero, S, Nigro, E, Del Vecchio, L, Di Noto, R, Cantisani, M, Colavita, I, Galdiero, Massimiliano, Cassiman, Jj, Daniele, Aurora, Pedone, C, Salvatore, F., Scudiero, Olga, Galdiero, Stefania, Nigro, Ersilia, Vecchio, L. D., Di Noto, R., Cantisani, M., Colavita, I., Galdiero, M., Cassiman, J. J., Daniele, A., Pedone, Carlo, Salvatore, Francesco |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
beta-Defensins
Cell Survival HUMAN BETA-DEFENSIN-3 DISULFIDE BONDS IMMUNE-SYSTEM PEPTIDES Cell Microbial Sensitivity Tests Biology Microbiology Anti-Infective Agents Cell Line Tumor beta defensin analogs human epithelial cell lines Enterococcus faecalis Escherichia coli medicine Humans Cytotoxic T cell Pharmacology (medical) Viability assay Mechanisms of Action: Physiological Effects Pharmacology Innate immune system Antimicrobial Infectious Diseases medicine.anatomical_structure Beta defensin Caco-2 Cell culture Pseudomonas aeruginosa Salts Caco-2 Cells |
| Popis: | Human beta-defensins (hBDs) are crucial peptides for the innate immune response and are thus prime candidates as therapeutic agents directed against infective diseases. Based on the properties of wild-type hBD1 and hBD3 and of previously synthesized analogs (1C, 3I, and 3N), we have designed a new analog, 3NI, and investigated its potential as an antimicrobial drug. Specifically, we evaluated the antimicrobial activities of 3NI versus those of hBD1, hBD3, 1C, 3I, and 3N. Our results show that 3NI exerted greater antibacterial activity against Pseudomonas aeruginosa , Escherichia coli , and Enterococcus faecalis than did hBD1 and hBD3, even with elevated salt concentrations. Moreover, its antiviral activity against herpes simplex virus 1 was greater than that of hBD1 and similar to that of hBD3. Subsequently, we investigated the cytotoxic effects of all peptides in three human epithelial carcinoma cell lines: A549 from lung, CaCo-2 from colon, and Capan-1 from pancreas. None of the analogs significantly reduced cell viability versus wild-type hBD1 and hBD3. They did not induce genotoxicity or cause an increase in the number of apoptotic cells. Using confocal microscopy, we also investigated the localization of the peptides during their incubation with epithelial cells and found that they were distributed on the cell surface, from which they were internalized. Finally, we show that hBD1 and hBD3 are characterized by high resistance to serum degradation. In conclusion, the new analog 3NI seems to be a promising anti-infective agent, particularly given its high salt resistance—a feature that is relevant in diseases such as cystic fibrosis. |
| Databáze: | OpenAIRE |
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