A characterization of the modular nature of histone‐derived antimicrobial peptides

Abstract

We have investigated the bactericidal activity, specificity, and mechanism of a several antimicrobial peptides (AMPs) derived from histone H2A alone and combined into chimeric peptides. Relative antibacterial efficacy of these AMPs was determined using radial diffusion assays, and eukaryotic cytotoxicity assays indicate that these peptides demonstrate bacterial specificity. Confocal microscopy was used to determine the mechanism of action of the peptides. Parasin, buforin II, and buforin I are segments of the larger hipposin AMP. Buforin II can translocate membranes while parasin is a permeabilizing peptide. Buforin I and hipposin are larger peptides containing both parasin and buforin II segments, and both are permeabilizing peptides relatively unable to translocate the membrane. These findings suggest that the addition of a lytic fragment to an otherwise‐translocating peptide confers a lytic property. We further explored this hypothesis by studying a chimeric peptide of parasin and DesHDAP1, another peptide known to translocate effectively. This chimera was found to be more strongly bactericidal than either parasin or DesHDAP1 alone.

A Modular Approach to the Histone H2A Family of Antimicrobial Peptides

“…The other possibility, that BF1 operates through a combination of translocation and membrane permeabilization, would not be measured through our current set of assays, as the translocation assay would indicate a solely membrane permeabilizing mechanism. 48 However, this method is only qualitative, not quantitative. In the future, we hope to develop a quantitative assay that would be able to measure translocation and permeabilization simultaneously so that we could determine if a peptide had dual mechanisms.…”