Abstract
The killer peptide KP is a synthetic decapeptide derived from the sequence of the variable region of a recombinant yeast killer toxin-like microbicidal single-chain antibody. KP proved to exert significant activities against diverse microbial and viral pathogens through different mechanisms of action, but little is known of its effect on apicomplexan protozoa. The aim of the present study was to evaluate the in vitro activity of KP against Toxoplasma gondii, a globally widespread protozoan parasite of great medical interest. The effect of KP treatment and its potential mechanism of action on T. gondii were evaluated by various methods, including light microscopy, quantitative PCR, flow cytometry, confocal microscopy, and transmission electron microscopy. In the presence of KP, the number of T. gondii tachyzoites able to invade Vero cells and the parasite intracellular proliferation were significantly reduced. Morphological observation and analysis of apoptotic markers suggested that KP is able to trigger an apoptosis-like cell death in T. gondii. Overall, our results indicate that KP could be a promising candidate for the development of new anti-Toxoplasma drugs with a novel mechanism of action.
Highlights
Toxoplasmosis, a globally widespread zoonotic disease that affects a variety of mammals, including humans, is caused by Toxoplasma gondii, an obligate intracellular parasite estimated to infect at least one-third of the world population (Tenter et al, 2000; Flegr et al, 2014; Hill and Dubey, 2016)
KP Inhibits T. gondii Infection in Vero Cells. It was preliminarily verified by the MTT assay the lack of toxicity of KP on Vero cells
The effect of increasing concentrations of KP on T. gondii proliferation in Vero cells was investigated by light microscopy and real-time PCR
Summary
Toxoplasmosis, a globally widespread zoonotic disease that affects a variety of mammals, including humans, is caused by Toxoplasma gondii, an obligate intracellular parasite estimated to infect at least one-third of the world population (Tenter et al, 2000; Flegr et al, 2014; Hill and Dubey, 2016). A combination of pyrimethamine and sulfadiazine represents the gold-standard chemotherapy for toxoplasmosis. These compounds are highly effective against acute infection, but have many side effects; current chemotherapy is not completely effective in eradicating encysted bradyzoites and in treating congenital toxoplasmosis (Montazeri et al, 2017). Alternative therapeutic compounds, with novel mechanisms of action against T. gondii and non-toxic, are needed
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