Anti-Toxoplasma gondii Effects of a Novel Spider Peptide XYP1 In Vitro and In Vivo

Yuan Liu,Shuaiqin Huang,Mengqi Wu,Xiaohua Liu,Yaqin Tang,Liping Jiang,Shengjie Hou,Xing Tang,Jing Li,Meichun Deng

doi:10.3390/biomedicines9080934

Yuan Liu, Shuaiqin Huang + Show 8 more

Open Access

https://doi.org/10.3390/biomedicines9080934

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Abstract

Toxoplasmosis, caused by an obligate intracellular parasite Toxoplasma gondii, is one of the most prevalent zoonoses worldwide. Treatments for this disease by traditional drugs have shown numerous side effects, thus effective alternative anti-Toxoplasma strategies or drugs are urgently needed. In this study, a novel spider peptide, XYP1, was identified from the cDNA library of the venom gland of the spider Lycosa coelestis. Our results showed that XYP1 has potent anti-Toxoplasma activity in vitro and in vivo. Specifically, treatment with XYP1 significantly inhibited the viability, invasion and proliferation of tachyzoites with low cytotoxicity (IC50 = 38.79 μΜ) on human host cells, and increased the survival rate of mice acutely infected with T. gondii. Next, scanning electron microscopy, transmission electron microscopy and RNA sequencing were employed to further explore the functional mechanism of XYP1, and the results indicated that XYP1 causes membrane perforation, swelling and disruption of tachyzoites, which could be closely associated with differential expression of several membrane-associated proteins including HSP29. In conclusion, XYP1 may be a promising new drug candidate for the treatment of toxoplasmosis.

Highlights

Toxoplasma gondii (T. gondii), an obligate intracellular parasite, can infect humans and various warm-blooded animals and cause toxoplasmosis [1]
Bioinformatics analysis demonstrated that XYP1 has 7 net charges with theoretical isoelectric point of 10.48, hydrophobicity of 0.332, 50% non-polar amino acid residues, and its sequence identity with peptide XYP2, Lycosin-I, Lycotoxin
According to the wheel projection, XYP1 possessed hydrophobic phenylalanine (Phe, F), isoleucine (Ile, I), alanine (Ala, A), methionine (Met, M) and tryptophan (Trp, W) residues on the hydrophobic side, while the hydrophilic lysine (Lys, K) and aspartate (Asp, D) residue and the polar serine (Ser, S) residue were observed on the opposite side (Figure 1D)

Summary

Introduction

Toxoplasma gondii (T. gondii), an obligate intracellular parasite, can infect humans and various warm-blooded animals and cause toxoplasmosis [1]. For the prevention and treatment of toxoplasmosis, there are many difficulties and bottlenecks in the development of anti-toxoplasmosis vaccines and drugs. There is still no approved vaccine for human toxoplasmosis, and for the control of toxoplasmosis mainly rely on sulfadiazine (SFZ), pyrimethamine and acetylspiramycin [4,5]. These traditional drugs have several problems including high toxicity, side effects, drug resistance, etc. The development of new alternative therapeutic options or drugs against toxoplasmosis is urgently needed

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