Novel Activity of a Synthetic Decapeptide Against Toxoplasma gondii Tachyzoites

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.

Myrislignan Exhibits Activities Against Toxoplasma gondii RH Strain by Triggering Mitochondrial Dysfunction

“…Currently, the treatment drugs for toxoplasmosis include clindamycin, azithromycin, sulfadiazine, pyrimethamine, and atovaquone. To date, the combination of pyrimethamine and sulfadiazine is considered as the frontline treatment for toxoplasmosis (Giovati et al, 2018; Munera López et al, 2019). However, this treatment has several side effects (de-la-Torre et al, 2011), such as bone marrow arrest, hypersensitive reactions, agranulocytosis and megaloblastic anemia (Rothova et al, 1993; Bosch-Driessen et al, 2002; Guaraldo et al, 2018).…”

Killer yeasts exert anti-plasmodial activities against the malaria parasite Plasmodium berghei in the vector mosquito Anopheles stephensi and in mice

“…Healthy mice were inoculated using Pb GFP CON -infected blood of a donor mouse previously incubated for 90 min at 25 °C with Wa F17.12-KT + (100 µg/ml KT), Wa F17.12-KT + (100 µg/ml KT) and mAbKT4, or PBS (control). Five days after inoculations, parasitaemia of the recipient mice ( n = 5 per group) was evaluated and mean values ± SEM, calculated as reported in Bonkian et al [34], are reported. The experiment was repeated twice.…”

“…In fact, β-1,3-glucans are microbial cell wall components in charge of maintaining cell morphology and osmotic integrity [33]. Nevertheless, KT action could involve also different pathways, as a recent study reported the apoptotic activity of peptides mimicking KTs against the protozoan parasite Toxoplasma gondii [34]. However, further investigations on human malaria parasites are requested to assess the mechanism of action of KTs.…”

Antimicrobial peptides – Advances in development of therapeutic applications

“…Besides, there are some other mechanisms include intracellular targets, such as inducing necrotic and apoptotic-like processes, inhibiting mitochondrial ATP synthesis or causing bioenergetics exhaustion [ 46 ]. Moreover, some AMPs interestingly showed the ability to interact selectively with infected enthythrocytes over host cell [ [47] , [48] , [49] ]. Therefore, AMPs represented a new class of peptide inhibitors that can possibly not only block the attachment and entry of human pathogenic protozoa and viruses but also prevent their growth and replication in the host cells.…”