Tityus serrulatus (Scorpion): From the Crude Venom to the Construction of Synthetic Peptides and Their Possible Therapeutic Application Against Toxoplasma gondii Infection

Abstract

Toxoplasmosis, caused by Toxoplasma gondii, is a major public concern owing to its neurotropic nature and high morbidity and mortality rates in immunocompromised patients and newborns. Current treatment for this disease is inefficient and produces side effects. Inflammatory mediators produced during T. gondii infection (e.g., cytokines and nitric oxide) are crucial in controlling parasite replication. In this context, Tityus serrulatus venom (TsV) induces the production of inflammatory mediators by immune cells. Thus, this study aimed to isolate and identify the components of TsV with potential anti-T. gondii activity. TsV was extracted from scorpions and lyophilized or loaded onto a column to obtain its fractions. TsV subfractions were obtained using chromatography, and its amino acid sequence was identified and applied to peptide design using bioinformatics tools. The C57BL/6 mice and their harvested macrophages were used to test the anti-Toxoplasma activity of TsV components and peptides. TsV and its fraction F6 attenuated the replication of tachyzoites in macrophages and induced nitric oxide and cytokine (IL-12, TNF, and IL-6) production by infected cells, without host cell toxicity. Moreover, Su6-B toxin, a subfraction of F6, demonstrated anti-T. gondii activity. The partially elucidated and characterized amino acid sequence of Sub6-B demonstrated 93% similarity with T. serrulatus 2 toxin (Ts2). Ts2 mimetic peptides (“Pep1,” “Pep2a,” and “Pep2b”) were designed and synthesized. Pep1 and Pep2a, but not Pep2b, reduced the replication of tachyzoites in macrophages. In vivo, treatment of T. gondii-infected mice with Pep1, Pep2a, or Pep2b decreased the number of cerebral cysts and did not induce hepatotoxicity in the animals. Taken together, our data show promising immunomodulatory and antiparasitic activity of TsV that could be explored and applied in future therapies for treating infectious parasitic diseases such as toxoplasmosis.

Animal venoms: a novel source of anti-Toxoplasma gondii drug candidates

“…Tityus serrulatus venom (TsV) is a mixture of active components from scorpion with immunomodulatory properties ( de Assis et al, 2021 ). It has been extensively studied for its pro-inflammatory, T-lymphocyte activation which can stimulate the expression of inflammatory factors, such as interleukins, tumor necrosis factor (TNF) and interferon-γ (IFN-γ) ( Zoccal et al, 2011 ; Casella-Martins et al, 2015 ).…”

“…It has been extensively studied for its pro-inflammatory, T-lymphocyte activation which can stimulate the expression of inflammatory factors, such as interleukins, tumor necrosis factor (TNF) and interferon-γ (IFN-γ) ( Zoccal et al, 2011 ; Casella-Martins et al, 2015 ). De Assis et al (2021) extracted scorpion venom and distilled using chromatography to obtain seven subgroups (F1, F2, F3, F4, F5, F6, and F7). About the anti- T. gondii activity in vitro of these seven subgroups, only F6 and F7 induced nitric oxide (NO) production in macrophages (MOs) at safe concentrations and exerted biological activity.…”

“…Animal venoms suppress T. gondii through upregulating the expression of pro-inflammatory factors. Different concentrations of TsV promoted the expression of IL-12, IL-6 and TNF-α ( de Assis et al, 2021 ). IL-6 is an important molecule in the inhibition of parasite growth.…”

Bioactive Peptides against Human Apicomplexan Parasites

“…There is only one study reporting peptide efficacy against T. gondii tissue cysts. The venom of the scorpion Tityus serrulatus was evaluated, and the Pep 1 peptide decreased the number of cerebral tissue cysts in infected mice, although its mechanism of action is still unknown [ 72 , 73 , 74 ].…”

Peptides with Diverse Functions from Scorpion Venom: A Great Opportunity for the Treatment of a Wide Variety of Diseases

“…It has been recommended that Ts7 fraction from crude TsV contains components that are responsible for generating pro-inflammatory immune responses of T. cruzi -infected macrophages [ 55 ] . It has also been confirmed that TsV components can induce the production of inflammatory mediators by immune cells against Toxoplasma gondii activity [ 56 ] . Mesobuthus eupeus has shown considerable antimicrobial and antiviral activity.…”