title: Cell-Density Dependence of Host-Defense Peptide Activity and Selectivity in the Presence of Host Cells.
abstract: 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 effectively asses HDP selectivity.
authors.forename: Filippo
authors.initials: F
authors.lastname: Savini
authors.affiliation: Department of Biochemical Sciences "A. Rossi Fanelli", Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome , 00185 Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Luca
authors.forename: Alessio
authors.initials: A
authors.lastname: Bocedi
authors.forename: Renato
authors.initials: R
authors.lastname: Massoud
authors.affiliation: Department of Biotechnology, Chosun University , 501-759 Gwangju, Korea.
authors.forename: Yoonkyung
authors.initials: Y
authors.lastname: Park
authors.affiliation: Department of Biochemical Sciences "A. Rossi Fanelli", Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome , 00185 Rome, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Mangoni
authors.forename: Lorenzo
authors.identifier: 0000-0002-5489-7381
authors.initials: L
authors.lastname: Stella
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D018407:Bacterial Physiological Phenomena / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000382:microbiology* / Q000473:pathology; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D006461:Hemolysis / Q000187:drug effects; D054884:Host-Pathogen Interactions; D006801:Humans; D008958:Models, Molecular
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides