ArticleAntimicrobial agents and chemotherapy2007
A novel Giardia lamblia nitroreductase, GlNR1, interacts with nitazoxanide and other thiazolides.
Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 89 citations in OpenAlex.
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- Investigating Antiprotozoal Chemotherapies with Novel Proteomic Tools-Chances and Limitations: A Critical Review.International journal of molecular sciences · 2024Review
- Fused Enzyme Glucose-6-Phosphate Dehydrogenase::6-Phosphogluconolactonase (G6PD::6PGL) as a Potential Drug Target inMicroorganisms · 2024Review
- New nitazoxanide derivatives: design, synthesis, biological evaluation, and molecular docking studies as antibacterial and antimycobacterial agents.RSC medicinal chemistry · 2023Article
- Nitazoxanide Inhibits the Bifunctional Enzyme GlG6PD::6PGL ofInternational journal of molecular sciences · 2023Article
- Ultrastructural Alterations of the Human PathogenPathogens (Basel, Switzerland) · 2023Review
- Heterologous Expression and Characterization of a Full-length Protozoan Nitroreductase from Leishmania orientalis isolate PCM2.Molecular biotechnology · 2023Article
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- Antigiardial Activity of Novel Guanidine Compounds.ChemMedChem · 2022Article
- Unusual Cell Structures and Organelles inMicroorganisms · 2022Review
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- A determination of pan-pathogen antimicrobials?Medicine in drug discovery · 2022Review
- An Overview of Mucosa-Associated Protozoa: Challenges in Chemotherapy and Future Perspectives.Frontiers in cellular and infection microbiology · 2022Review
- Synthesis and antiplasmodial assessment of nitazoxanide and analogs as new antimalarial candidates.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2022Article
- Promising proteins detected by Western blot from Echinococcus granulosus protoscoleces for predicting early post-surgical outcomes in CE-affected Tunisian children.Parasites & vectors · 2021Article
- Nitroreductase Activites inPathogens (Basel, Switzerland) · 2021Article
- Nitroreductases of bacterial origin in Giardia lamblia: Potential role in detoxification of xenobiotics.MicrobiologyOpen · 2019Article
- Oxygen induces the expression of invasion and stress response genes in the anaerobic salmon parasite Spironucleus salmonicida.BMC biology · 2019Article
- Genetic variation in metronidazole metabolism and oxidative stress pathways in clinicalInfection and drug resistance · 2019Article
- Differential protein expression and post-translational modifications in metronidazole-resistant Giardia duodenalis.GigaScience · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nitrothiazole analogue nitazoxanide [NTZ; 2-acetolyloxy-N-(5-nitro-2-thiazolyl)benzamide] represents the parent compound of a class of drugs referred to as thiazolides and exhibits a broad spectrum of activities against a wide variety of helminths, protozoa, and enteric bacteria infecting animals and humans. NTZ and other thiazolides are active against a wide range of other intracellular and extracellular protozoan parasites in vitro and in vivo, but their mode of action and respective subcellular target(s) have only recently been investigated. In order to identify potential targets of NTZ and other thiazolides in Giardia lamblia trophozoites, we have developed an affinity chromatography system using the deacetylated derivative of NTZ, tizoxanide (TIZ), as a ligand. Affinity chromatography on TIZ-agarose using cell extracts of G. lamblia trophozoites resulted in the isolation of an approximately 35-kDa polypeptide, which was identified by mass spectrometry as a nitroreductase (NR) homologue (EAA43030.1). NR was overexpressed as a six-histidine-tagged recombinant protein in Escherichia coli, purified, and then characterized using an assay for oxygen-insensitive NRs with dinitrotoluene as a substrate. This demonstrated that the NR was functionally active, and the protein was designated GlNR1. In this assay system, NR activity was severely inhibited by NTZ and other thiazolides, demonstrating that the antigiardial activity of these drugs could be, at least partially, mediated through inhibition of GlNR1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.