Cell-density dependence of host-defense peptide activity and selectivity in the presence of host cells
| Autor: | Yoonkyung Park, Vincenzo Luca, Maria Luisa Mangoni, Filippo Savini, Lorenzo Stella, Renato Massoud, Alessio Bocedi |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Models Molecular Cell type Erythrocytes Cell Peptide Biology Animals Anti-Bacterial Agents Antimicrobial Cationic Peptides Bacteria Bacterial Infections Bacterial Physiological Phenomena Escherichia coli Escherichia coli Infections Hemolysis Humans Host-Pathogen Interactions 01 natural sciences Biochemistry 03 medical and health sciences Models medicine Settore BIO/10 Settore CHIM/02 - Chimica Fisica chemistry.chemical_classification 010405 organic chemistry Settore BIO/12 Molecular General Medicine biology.organism_classification In vitro 0104 chemical sciences 030104 developmental biology medicine.anatomical_structure chemistry Partition equilibrium Toxicity Molecular Medicine Selectivity |
| Popis: | Host-defense peptides (HDPs) are promising compounds against multidrug-resistant microbes. In vitro, their bactericidal and toxic concentrations are significantly different, but this might be due to the use of separate assays, with different cell densities. For experiments with a single cell type, the cell-density dependence of the active concentration of the DNS-PMAP23 HDP could be predicted based on the water/cell-membrane partition equilibrium and exhibited a lower bound at low cell counts. On the basis of these data, in the simultaneous presence of both bacteria and an excess of human cells, one would expect no significant toxicity, but also inhibition of the bactericidal activity due to peptide sequestration by host cells. However, this inhibition did not take place in assays with mixed cell populations, showing that for the HDP esculentin-1a(1–21)NH2, a range of bactericidal, nontoxic concentrations exists and confirming the effective selectivity of HDPs. Mixed-cell assays might be necessary to effe... |
| Databáze: | OpenAIRE |
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