A Modular Approach to the Histone H2A Family of Antimicrobial Peptides

Abstract

Hipposin and buforin II (BF2) are naturally occurring antimicrobial peptides (AMPs). Although BF2 is essentially identical to the middle section of hipposin, BF2 is a membrane translocating peptide and hipposin is a membrane permeabilizing peptide. To investigate this difference, we compared the structure, antimicrobial activity, translocating ability, and membrane permeabilizing ability of hipposin, BF2, parasin (analogous to the N‐terminal section of hipposin), and buforin I (essentially parasin plus BF2). Hipposin and BF2 had the highest activities against bacteria, followed by buforin I then parasin. Cellular permeabilization assays demonstrated that hipposin, buforin I, and parasin all display membrane permeabilizing ability, while translocation assays showed that only BF2 was membrane translocating. These observations imply that the addition of the parasin fragment to BF2 alters its antibacterial mechanism. Ongoing studies are examining the activity and mechanisms of other portions of the hipposin peptide.