Trichomonads, hydrogenosomes and drug resistance
Trichomonas vaginalis and Tritrichomonas foetus are sexually transmitted pathogens of the genito-urinary tract of humans and cattle, respectively. These organisms are amitochondrial anaerobes possessing hydrogenosomes, double membrane-bound organelles involved in catabolic processes extending glycolysis. The oxidative decarboxylation of pyruvate in hydrogenosomes is coupled to ATP synthesis and linked to ferredoxin-mediated electron transport. This pathway is responsible for metabolic activation of 5-nitroimidazole drugs, such as metronidazole, used in chemotherapy of trichomoniasis. Prolonged cultivation of trichomonads under sublethal pressure of metronidazole results in development of drug resistance. In both pathogenic species the resistance develops in a multistep process involving a sequence of stages that differ in drug susceptibility and metabolic activities. Aerobic resistance, similar to that occurring in clinical isolates of T. vaginalis from treatment-refractory patients, appears as the earliest stage. The terminal stage is characterised by stable anaerobic resistance at which the parasites show very high levels of minimal lethal concentration for metronidazole under anaerobic conditions (approximately 1000 microg m...Continue Reading
Uptake of metronidazole and its effect on viability in trichomonads and Entamoeba invadens under anaerobic and aerobic conditions
Pyruvate kinase from Trichomonas vaginalis, an allosteric enzyme stimulated by ribose 5-phosphate and glycerate 3-phosphate
Presence of a fructose-2,6-bisphosphate-insensitive pyrophosphate: fructose-6-phosphate phosphotransferase in the anaerobic protozoa Tritrichomonas foetus, Trichomonas vaginalis and Isotricha prostoma
Metronidazole radical anion generation in vivo in Trichomonas vaginalis: oxygen quenching is enhanced in a drug-resistant strain
Nitroimidazole and oxygen derived radicals detected by electron spin resonance in hydrogenosomal and cytosolic fractions from Trichomonas vaginalis
In vitro drug susceptibility and doses of metronidazole required for cure in cases of refractory vaginal trichomoniasis
Ferredoxin-dependent reduction of nitroimidazole derivatives in drug-resistant and susceptible strains of Trichomonas vaginalis
13C-NMR reveals glycerol as an unexpected major metabolite of the protozoan parasite Trichomonas vaginalis
Metronidazole inhibition of hydrogen production in vivo in drug-sensitive and resistant strains of Trichomonas vaginalis
Metabolic differences between metronidazole resistant and susceptible strains of Tritrichomonas foetus
Metronidazole resistance of Trichomonas vaginalis as a cause of treatment failure in trichomoniasis--A case report
Primary structure and eubacterial relationships of the pyruvate:ferredoxin oxidoreductase of the amitochondriate eukaryote Trichomonas vaginalis
Primary structure of the hydrogenosomal malic enzyme of Trichomonas vaginalis and its relationship to homologous enzymes
Molecular characterization of the alpha-subunit of Trichomonas vaginalis hydrogenosomal succinyl CoA synthetase
Purification and partial characterization of malate dehydrogenase (decarboxylating) from Tritrichomonas foetus hydrogenosomes
Identification, purification and separation of different isozymes of NADP-specific malic enzyme from Tritrichomonas foetus
Small subunit ribosomal RNA+ of Hexamita inflata and the quest for the first branch in the eukaryotic tree
Identification and characterization of [Fe]-hydrogenases in the hydrogenosome of Trichomonas vaginalis
Presence of a mitochondrial-type 70-kDa heat shock protein in Trichomonas vaginalis suggests a very early mitochondrial endosymbiosis in eukaryotes
Iron-ascorbate cleavable malic enzyme from hydrogenosomes of Trichomonas vaginalis: purification and characterization
Targeting and translocation of proteins into the hydrogenosome of the protist Trichomonas: similarities with mitochondrial protein import
Susceptibility in vitro of clinically metronidazole-resistant Trichomonas vaginalis to nitazoxanide, toyocamycin, and 2-fluoro-2'-deoxyadenosine
Deep sequencing of Trichomonas vaginalis during the early infection of vaginal epithelial cells and amoeboid transition
In vivo expression of ferredoxin in a drug resistant trichomonad increases metronidazole susceptibility
Effects of metronidazole and tinidazole on NTPDase1 and ecto-5'-nucleotidase from intact cells of Trichomonas vaginalis
Mitochondrial type iron-sulfur cluster assembly in the amitochondriate eukaryotes Trichomonas vaginalis and Giardia intestinalis, as indicated by the phylogeny of IscS
Documentation of in vivo and in vitro aerobic resistance of feline Tritrichomonas foetus isolates to ronidazole
Hydrogenosome metabolism is the key target for antiparasitic activity of resveratrol against Trichomonas vaginalis
Giardia, Entamoeba, and Trichomonas enzymes activate metronidazole (nitroreductases) and inactivate metronidazole (nitroimidazole reductases)
Pyruvate decarboxylase, the target for omeprazole in metronidazole-resistant and iron-restricted Tritrichomonas foetus
5-Nitroimidazole drugs effective against metronidazole-resistant Trichomonas vaginalis and Giardia duodenalis
Current therapeutics, their problems, and sulfur-containing-amino-acid metabolism as a novel target against infections by "amitochondriate" protozoan parasites
Use of Trichomonas vaginalis clinical isolates to evaluate correlation of gene expression and metronidazole resistance
Photodynamic therapy in the cattle protozoan Tritrichomonas foetus cultivated on superhydrophilic carbon nanotube
Genetically different clonal isolates of Trichomonas gallinae, obtained from the same bird, can vary in their drug susceptibility, an in vitro evidence
Trichomonas vaginalis: metronidazole and other nitroimidazole drugs are reduced by the flavin enzyme thioredoxin reductase and disrupt the cellular redox system. Implications for nitroimidazole toxicity and resistance
The actin-based machinery of Trichomonas vaginalis mediates flagellate-amoeboid transition and migration across host tissue
Secondary alcohol dehydrogenase catalyzes the reduction of exogenous acetone to 2-propanol in Trichomonas vaginalis
Targeted gene replacement of a ferredoxin gene in Trichomonas vaginalis does not lead to metronidazole resistance
Toxicogenetic evaluation of metronidazole in the treatment of women infected with Trichomonas vaginalis
Hydrogenosomes of laboratory-induced metronidazole-resistant Trichomonas vaginalis lines are downsized while those from clinically metronidazole-resistant isolates are not
Alternative 2-keto acid oxidoreductases in Trichomonas vaginalis: artifact of histochemical staining
Down-regulation of flavin reductase and alcohol dehydrogenase-1 (ADH1) in metronidazole-resistant isolates of Trichomonas vaginalis
Unexpected properties of NADP-dependent secondary alcohol dehydrogenase (ADH-1) in Trichomonas vaginalis and other microaerophilic parasites
Trichomonas gypaetinii n. sp., a new trichomonad from the upper gastrointestinal tract of scavenging birds of prey
Characterization of a gene encoding alcohol dehydrogenase in benznidazole-susceptible and -resistant populations of Trypanosoma cruzi
Gradual neofunctionalization in the convergent evolution of trichomonad lactate and malate dehydrogenases
Evolution of Tumor Metabolism might Reflect Carcinogenesis as a Reverse Evolution process (Dismantling of Multicellularity)
An Efficient One-Pot Catalyzed Synthesis of 2,4-Disubstituted 5-Nitroimidazoles Displaying Antiparasitic and Antibacterial Activities
Efficacy of guar gum-based ronidazole capsules as a treatment for Tritrichomonas foetus infection in cats
In vitro activity of hexadecylphosphocholine (miltefosine) against metronidazole-resistant and -susceptible strains of Trichomonas vaginalis
Iron-induced changes in pyruvate metabolism of Tritrichomonas foetus and involvement of iron in expression of hydrogenosomal proteins
Structural basis of 5-nitroimidazole antibiotic resistance: the crystal structure of NimA from Deinococcus radiodurans
A systematic review of the literature on mechanisms of 5-nitroimidazole resistance in Trichomonas vaginalis
Antiparasitic activity of furanyl N-acylhydrazone derivatives against Trichomonas vaginalis: in vitro and in silico analyses
Incorporation of iron into Tritrichomonas foetus cell compartments reveals ferredoxin as a major iron-binding protein in hydrogenosomes
Diamine derivative anti-Trichomonas vaginalis and anti-Tritrichomonas foetus activities by effect on polyamine metabolism
Molecular Targets Implicated in the Antiparasitic and Anti-Inflammatory Activity of the Phytochemical Curcumin in Trichomoniasis.
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