Hp1404, a new antimicrobial peptide from the scorpion Heterometrus petersii.

Zhongjie Li,Luyang Cao,Lanxia Meng,Wenxin Li,Xiaobo Xu,Yingliang Wu,Zhijian Cao,Qian Zhang,Miguel A R B Castanho

doi:10.1371/journal.pone.0097539

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.

Highlights

The increasing frequency of antibiotic resistance among microorganisms is becoming a more and more serious problem, which has outpaced the development of new antibiotics [1,2,3]
Characterization and analysis of Hp1404 After systemic screening the clones from the venom gland cDNA library of the scorpion H. petersii, we obtained a new peptide
Multiple sequence alignment revealed that Hp1404 shared a high identity (Figure 1B) with the AMPs StCT1 [25], CT1-NDBP-5.17 [26], IsCT [27], StCT2 [28], OcyC2 [29], and pantinin 1 [30], which suggests that Hp1404 peptide may have antibacterial activity

Summary

Introduction

The increasing frequency of antibiotic resistance among microorganisms is becoming a more and more serious problem, which has outpaced the development of new antibiotics [1,2,3]. As a potential source of these agents, antimicrobial peptide (AMPs) are ubiquitous in nature, which can be found in microorganisms [4], insects [5], amphibians [6], mammals [7], and plants [8]. They are produced as a part of the innate immune system defense, and show potent antimicrobial activity against a broad spectrum of microorganisms including resistant strains [9]. Some of them can interfere with the intracellular processes, such as affecting cell-wall biosynthesis pathway, inhibiting protein biosynthesis, or interacting with nucleic acids [12] These properties make them the attractive candidates for the development of new antimicrobial agents in overcoming microbial resistance. At least 2300 different AMPs have been studied (http://aps.unmc.edu/AP/main.php) during the last three decades, and several AMPs have been investigated as therapeutic agents in the past decade [9]

Methods

Results

Conclusion