title: Entamoeba thiol-based redox metabolism: A potential target for drug development.
abstract: Amebiasis is an intestinal infection widespread throughout the world caused by the human pathogen Entamoeba histolytica. Metronidazole has been a drug of choice against amebiasis for decades despite its low efficacy against asymptomatic cyst carriers and emergence of resistance in other protozoa with similar anaerobic metabolism. Therefore, identification and characterization of specific targets is urgently needed to design new therapeutics for improved treatment against amebiasis. Toward this goal, thiol-dependent redox metabolism is of particular interest. The thiol-dependent redox metabolism in E. histolytica consists of proteins including peroxiredoxin, rubrerythrin, Fe-superoxide dismutase, flavodiiron proteins, NADPH: flavin oxidoreductase, and amino acids including l-cysteine, S-methyl-l-cysteine, and thioprolines (thiazolidine-4-carboxylic acids). E. histolytica completely lacks glutathione and its metabolism, and l-cysteine is the major intracellular low molecular mass thiol. Moreover, this parasite possesses a functional thioredoxin system consisting of thioredoxin and thioredoxin reductase, which is a ubiquitous oxidoreductase system with antioxidant and redox regulatory roles. In this review, we summarize and highlight the thiol-based redox metabolism and its control mechanisms in E. histolytica, in particular, the features of the system unique to E. histolytica, and its potential use for drug development against amebiasis.
authors.affiliation: Department of Parasitology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640, Japan.
authors.forename: Ghulam
authors.initials: G
authors.lastname: Jeelani
authors.affiliation: Department of Parasitology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640, Japan; Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8572, Japan. Electronic address: nozaki@nih.go.jp.
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Nozaki
mesh_terms: D000981:Antiprotozoal Agents / Q000627:therapeutic use; D003545:Cysteine / Q000031:analogs & derivatives / Q000378:metabolism; D004748:Entamoeba histolytica / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D004749:Entamoebiasis / Q000188:drug therapy / Q000469:parasitology*; D005420:Flavoproteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006422:Hemerythrin / Q000235:genetics / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012416:Rubredoxins / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053778:Thiazolidines / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism
chemical_list: D000981:Antiprotozoal Agents; D005420:Flavoproteins; D006422:Hemerythrin; D015800:Protozoan Proteins; D012416:Rubredoxins; D053778:Thiazolidines; C055857:rubrerythrins; D013879:Thioredoxins; C008425:S-methylcysteine; D054464:Peroxiredoxins; D013482:Superoxide Dismutase; D013880:Thioredoxin-Disulfide Reductase; D003545:Cysteine
keywords: Cysteine; Drug target; Entamoeba histolytica; Oxidative stress; Redox; Thiol