Abstract
We previously identified a novel antimicrobial peptide with a broad spectrum bactericidal activity from human hepatitis B virus (HBV) core protein (HBc) arginine-rich domain (ARD). We compared the antimicrobial activities of HBcARD peptides from different hepadnaviruses which share similar amino acid sequences. In general, mammalian HBcARD peptides exhibited stronger antimicrobial activity than avian peptides. Using the strategy of D-amino acid substitutions, we improved the antimicrobial efficacy of human HBcARD peptide. This D-HBcARD peptide was much more resistant than L-HBcARD peptide to proteolytic degradation in vitro. Moreover, this D-HBcARD peptide maintained similar minimal bactericidal concentrations (MBC) against tested bacteria, and showed very low hemolytic activity. In the Staphylococcus aureus-infected mouse model, this D-HBcARD peptide was more protective than the L-HBcARD peptide. Repeated treatments with either L- or D-HBcARD peptides induced no significant immunogenicity. New derivatives of HBcARD peptides could serve as alternatives to the conventional antibiotics in clinical medicine in the future.
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Acknowledgment
This research was supported by Academia Sinica and the Ministry of Science and Technology (MOST 104-2325-B-001-002-, MOST 104-0210-01-09-02, and MOST 105-0210-01-13-01), Taiwan. We are grateful to Dr. Kai-Chih Chang for the bacterial strains. HLC was funded by a postdoctoral fellowship from Academia Sinica, Taiwan.
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All animal experiments were conducted under protocols approved by Academia Sinica Institutional Animal Care & Utilization Committee (ASIACUC permit number 12–02-322). Research was conducted in compliance with the principles stated in the Guide for the Care and Use of Laboratory Animals, National Research Council, 1996.
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Chen, HL., Su, PY. & Shih, C. Improvement of in vivo antimicrobial activity of HBcARD peptides by D-arginine replacement. Appl Microbiol Biotechnol 100, 9125–9132 (2016). https://doi.org/10.1007/s00253-016-7621-6
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DOI: https://doi.org/10.1007/s00253-016-7621-6