title: Potential of novel antimicrobial peptide P3 from bovine erythrocytes and its analogs to disrupt bacterial membranes in vitro and display activity against drug-resistant bacteria in a mouse model.
abstract: With the emergence of many antibiotic-resistant strains worldwide, antimicrobial peptides (AMPs) are being evaluated as promising alternatives to conventional antibiotics. P3, a novel hemoglobin peptide derived from bovine erythrocytes, exhibited modest antimicrobial activity in vitro. We evaluated the antimicrobial activities of P3 and an analog, JH-3, both in vitro and in vivo. The MICs of P3 and JH-3 ranged from 3.125 μg/ml to 50 μg/ml when a wide spectrum of bacteria was tested, including multidrug-resistant strains. P3 killed bacteria within 30 min by disrupting the bacterial cytoplasmic membrane and disturbing the intracellular calcium balance. Circular dichroism (CD) spectrometry showed that P3 assumed an α-helical conformation in bacterial lipid membranes, which was indispensable for antimicrobial activity. Importantly, the 50% lethal dose (LD50) of JH-3 was 180 mg/kg of mouse body weight after intraperitoneal (i.p.) injection, and no death was observed at any dose up to 240 mg/kg body weight following subcutaneous (s.c.) injection. Furthermore, JH-3 significantly decreased the bacterial count and rescued infected mice in a model of mouse bacteremia. In conclusion, P3 and an analog exhibited potent antimicrobial activities and relatively low toxicities in a mouse model, indicating that they may be useful for treating infections caused by drug-resistant bacteria.
authors.affiliation: Key Discipline Open Laboratory of Animal Viral Disease Control and Residual Analysis of Henan Province, Department of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Discipline Open Laboratory of Animal Viral Disease Control and Residual Analysis of Henan Province, Department of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China hujianhe@hist.edu.cn haoxyz@163.com.
authors.forename: Yanzhao
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Key Discipline Open Laboratory of Animal Viral Disease Control and Residual Analysis of Henan Province, Department of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Key Discipline Open Laboratory of Animal Viral Disease Control and Residual Analysis of Henan Province, Department of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China.
authors.forename: Bolin
authors.initials: B
authors.lastname: Hang
authors.affiliation: Key Discipline Open Laboratory of Animal Viral Disease Control and Residual Analysis of Henan Province, Department of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Key Discipline Open Laboratory of Animal Viral Disease Control and Residual Analysis of Henan Province, Department of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Wei
authors.affiliation: Key Discipline Open Laboratory of Animal Viral Disease Control and Residual Analysis of Henan Province, Department of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China hujianhe@hist.edu.cn haoxyz@163.com.
authors.forename: Jianhe
authors.initials: J
authors.lastname: Hu
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology; D002176:Candida albicans / Q000187:drug effects; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects; D002942:Circular Dichroism; D024901:Drug Resistance, Multiple, Bacterial; D004912:Erythrocytes / Q000737:chemistry*; D004926:Escherichia coli / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides