Dataset Information

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.

SUBMITTER: Yason JA

PROVIDER: S-EPMC6105778 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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

Yason John Anthony JA Koh Kristine Anne Ru Ping KARP Tan Kevin Shyong Wei KSW

Antimicrobial agents and chemotherapy 20180727 8

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, ...[more]

PMID: 29866860

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Project description:BACKGROUND:Blastocystis sp. is a common protozoan parasite frequently identified in the digestive tract of humans and a large variety of animal hosts worldwide, including birds. It exhibits a large genetic diversity with the identification of 17 subtypes (STs), most of them with low host specificity. ST6 and ST7 were identified in birds and suggested to represent avian STs only in the context of scarce small-scale epidemiological surveys. Moreover, these two STs also account for a significant proportion of human infections whose zoonotic origin has never been clearly confirmed. Therefore, molecular screening of Blastocystis sp. was conducted by quantitative real-time PCR for fecal samples from poultry farms and their in-contact humans from slaughterhouses in Lebanon. In parallel, a control group consisting of patients hospitalized in the same geographical area and reporting no contact with poultry was also screened for the presence of the parasite. RESULTS:The overall prevalence of Blastocystis sp. was shown to reach around 32% in chicken samples and 65% in the farms screened. All the avian isolates were subtyped and belonged to either ST6 or ST7, with a large predominance of ST6. Fifty-four percent of slaughterhouse staff members were positive for Blastocystis sp. compared with a similar prevalence of 56% in hospitalized patients. ST3 was predominant in both human cohorts followed by either ST1 then ST2 among slaughterhouse staff or by ST2 then ST1 among hospitalized patients. ST6 was also identified in two slaughterhouse workers and not in the group of hospitalized patients. Gene sequence identity was observed between chicken and human ST6 isolates from the same slaughterhouse. CONCLUSIONS:Our data revealed a high prevalence of Blastocystis sp. in chicken samples and confirmed that ST6 and ST7 represented avian-adapted STs. Among both human cohorts, Blastocystis sp. infection was shown to exceed 50% with a predominance of ST3. The identification of ST6 in slaughterhouse staff members confirmed the zoonotic transmission of this ST through repeated and direct contact between chickens and their handlers.

Dataset Information

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

Publications

Viability Screen of LOPAC<sup>1280</sup> Reveals Phosphorylation Inhibitor Auranofin as a Potent Inhibitor of Blastocystis Subtype 1, 4, and 7 Isolates.

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