Modular Analysis of Hipposin, a Histone-Derived Antimicrobial Peptide Consisting of Membrane Translocating and Membrane Permeabilizing Fragments

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Antimicrobial peptides continue to garner attention as potential alternatives to conventional antibiotics. Hipposin is a histone-derived antimicrobial peptide (HDAP) that was previously isolated from Atlantic halibut. Though its potency against several bacterial strains has been documented, its antibacterial mechanism had not been characterized. The mechanism of this peptide is particularly interesting to consider since the full hipposin sequence contains the sequences of parasin and buforin II (BF2), two other known antimicrobial peptides that act via different antibacterial mechanisms. While parasin kills bacteria by inducing membrane permeabilization, buforin II enters cells without causing significant membrane disruption, harming bacteria through interactions with intracellular nucleic acids. In this study, we used a modular approach to characterize hipposin and determine the role of the parasin and buforin II fragments in the overall hipposin mechanism. Our results show that hipposin kills bacteria by inducing membrane permeabilization, and this membrane permeabilization is promoted by the presence of the N-terminal parasin domain. Portions of hipposin lacking the parasin sequence do not cause membrane permeabilization and function more similarly to buforin II. We also determined that the C-terminal portion of hipposin, HipC, is a cellpenetrating peptide that readily enters bacterial cells but has no measurable antimicrobial activity. HipC is the first membrane active histone fragment identified that does not kill bacterial or eukaryotic cells. Together, these results not only characterize hipposin but also provide a useful starting point for considering the activity of chimeric peptides made by combining peptides that operate via differing mechanisms.


Published: Biochimica et Biophysica Acta (BBA) - Biomembranes

Volume 1838, Issue 9, September 2014, Pages 2228–2233.



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