In vitro susceptibility of human Blastocystis subtypes to simeprevir.

Autor:	Mossallam SF; Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria, Egypt., El-Mansoury SAT; Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria, Egypt., Tolba MM; Department of Parasitology, Medical Research Institute, Alexandria University, Alexandria, Egypt., Kohla AA; Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria, Egypt., Khedr SI; Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Jazyk:	angličtina
Zdroj:	Saudi journal of biological sciences [Saudi J Biol Sci] 2021 Apr; Vol. 28 (4), pp. 2491-2501. Date of Electronic Publication: 2021 Feb 02.
DOI:	10.1016/j.sjbs.2021.01.050
Abstrakt:	Introduction and Aim: Blastocystis is a common enteric parasite, having a worldwide distribution. Many antimicrobial agents are effective against it, yet side effects and drug resistance have been reported. Thus, ongoing trials are being conducted for exploring anti- Blastocystis alternatives. Proteases are attractive anti-protozoal drug targets, having documented roles in Blastocystis . Serine proteases are present in both hepatitis C virus and Blastocystis . Since drug repositioning is quite trendy, the in vitro efficacy of simeprevir (SMV), an anti-hepatitis serine protease inhibitor, against Blastocystis was investigated in the current study. Methods: Stool samples were collected from patients, Alexandria, Egypt. Concentrated stools were screened using direct smears, trichrome, and modified Ziehl-Neelsen stains to exclude parasitic co-infections. Positive stool isolates were cultivated, molecularly subtyped for assessing the efficacy of three SMV doses (100,150, and 200 μg/ml) along 72 hours (h), on the most common subtype, through monitoring parasite growth, viability, re-culture, and also via ultrastructure verification. The most efficient dose and duration were later tested on other subtypes. Results: Results revealed that Blastocystis was detected in 54.17% of examined samples. Molecularly, ST3 predominated (62%), followed by ST1 (8.6%) and ST2 (3.4%). Ascending concentrations of SMV progressively inhibited growth, viability, and re-culture of treated Blastocystis , with a non-statistically significant difference when compared to the therapeutic control metronidazole (MTZ). The most efficient dose and duration against ST3 was 150 µg/ml for 72 h. This dose inhibited the growth of ST3, ST1, and ST2 with percentages of 95.19%, 94.83%, and 94.74%, successively and viability with percentages of 98.30%, 98.09%, and 97.96%, successively. This dose abolished Blastocystis upon re-culturing. Ultra-structurally, SMV induced rupture of Blastocystis cell membrane leading to necrotic death, versus the reported apoptotic death caused by MTZ. In conclusion, 150 µg/ml SMV for 72 h proved its efficacy against ST1, ST2, and ST3 Blastocystis , thus sparing the need for pre-treatment molecular subtyping in developing countries. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2021 The Author(s).)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu