Viability Screen of LOPAC1280 Reveals Phosphorylation Inhibitor Auranofin as a Potent Inhibitor of Blastocystis Subtype 1, 4, and 7 Isolates.

Abstract

Blastocystis is an enteric parasite with extensive global prevalence. Studies have linked infection with this protist with a variety of gastrointestinal disorders, including irritable bowel syndrome. Due to the polymorphic nature of Blastocystis, studies on the parasite could be complicated, as results can be easily misinterpreted. Metronidazole is the commonly prescribed drug for Blastocystis infection, although there have been increasing reports of drug resistance. Hence, there is a need to identify alternative drugs to eliminate Blastocystis infection. In this study, LOPAC1280 was screened and drugs that can decrease the viability of three Blastocystis isolates in cultures were identified. Using apoptosis assay and imaging flow cytometry, phenotypic changes in Blastocystis cells after treatment were also analyzed to obtain insights into the possible mechanism of action of these drugs. Three drugs-diphenyleneiodonium chloride, auranofin, and BIX 01294 trihydrochloride hydrate-were effective against all three isolates tested. Repurposing of these drugs for Blastocystis treatment could be a way of combating metronidazole resistance relatively quickly and at a lower cost.