Hp1404, a new antimicrobial peptide from the scorpion Heterometrus petersii

Zhongjie Li; Xiaobo Xu; Lanxia Meng; Qian Zhang; Luyang Cao; Wenxin Li; Yingliang Wu; Zhijian Cao

doi:10.1371/journal.pone.0097539

Hp1404, a new antimicrobial peptide from the scorpion Heterometrus petersii

PLoS One. 2014 May 14;9(5):e97539. doi: 10.1371/journal.pone.0097539. eCollection 2014.

Authors

Zhongjie Li¹, Xiaobo Xu¹, Lanxia Meng¹, Qian Zhang¹, Luyang Cao¹, Wenxin Li¹, Yingliang Wu¹, Zhijian Cao¹

Affiliation

¹ State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, PR China.

Abstract

Antimicrobial peptides have attracted much interest as a novel class of antibiotics against a variety of microbes including antibiotics resistant strains. In this study, a new cationic antimicrobial peptide Hp1404 was identified from the scorpion Heterometrus petersii, which is an amphipathic α-helical peptide and has a specific inhibitory activity against gram-positive bacteria including methicillin-resistant Staphylococcus aureus. Hp1404 can penetrate the membrane of S. aureus at low concentration, and disrupts the cellular membrane directly at super high concentration. S. aureus does not develop drug resistance after multiple treatments with Hp1404 at sub MIC concentration, which is possibly associated with the antibacterial mechanism of the peptide. In addition, Hp1404 has low toxicity to both mammalian cells (HC₅₀ = 226.6 µg/mL and CC₅₀ > 100 µg/mL) and balb-c mice (Non-toxicity at 80 mg/Kg by intraperitoneal injection and LD₅₀ = 89.8 mg/Kg by intravenous injection). Interestingly, Hp1404 can improve the survival rate of the MRSA infected balb-c mice in the peritonitis model. Taken together, Hp1404 may have potential applications as an antibacterial agent.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Anti-Bacterial Agents / biosynthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / isolation & purification*
Anti-Bacterial Agents / pharmacology
Antimicrobial Cationic Peptides / biosynthesis
Antimicrobial Cationic Peptides / chemistry
Antimicrobial Cationic Peptides / isolation & purification*
Antimicrobial Cationic Peptides / pharmacology
Cell Survival / drug effects
Escherichia coli / genetics
Escherichia coli / metabolism
Female
Gene Expression
HEK293 Cells
Humans
Injections, Intraperitoneal
Injections, Intravenous
Lethal Dose 50
Methicillin-Resistant Staphylococcus aureus / drug effects
Methicillin-Resistant Staphylococcus aureus / growth & development
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Peritonitis / drug therapy*
Peritonitis / microbiology
Peritonitis / mortality
Protein Structure, Secondary
Recombinant Proteins / biosynthesis
Recombinant Proteins / chemistry
Recombinant Proteins / genetics
Recombinant Proteins / pharmacology
Scorpions / chemistry*
Scorpions / immunology
Staphylococcal Infections / drug therapy*
Staphylococcal Infections / microbiology
Staphylococcal Infections / mortality
Survival Analysis

Substances

Anti-Bacterial Agents
Antimicrobial Cationic Peptides
Recombinant Proteins

Grants and funding

This work is supported by the grants from National Key Basic Research Program in China (http://www.973.gov.cn/English/AreaList.aspx): Nos. 2010CB529800, and 2010CB530100. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.