ArticleInternational journal for parasitology. Drugs and drug resistance2015
A single mutation in the gatekeeper residue in TgMAPKL-1 restores the inhibitory effect of a bumped kinase inhibitor on the cell cycle.
Article in International journal for parasitology. Drugs and drug resistance, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- Affino-Proteomic Analysis of Bumped Kinase Inhibitor BKI-1708 inMicroorganisms · 2026Article
- Chemical genetics reveals Leishmania KKT2 and CRK9 kinase activity is required for cell cycle progression.PLoS pathogens · 2026Article
- Bumped Kinase Inhibitor BKI-1708 Interferes in Cytokinesis and Drives Baryzoite Conversion in the Cyst-Forming Apicomplexan ParasitesInternational journal of molecular sciences · 2026Article
- The PP2A-2 holoenzyme orchestrates daughter cell emergence during cytokinesis in Toxoplasma gondii.PLoS pathogens · 2025Article
- Bumped Kinase Inhibitors Inhibit bothACS infectious diseases · 2025Article
- Versatile Imidazole Scaffold with Potent Activity against Multiple Apicomplexan Parasites.ACS infectious diseases · 2025Article
- Treatment with BKI-1748 afterAntimicrobial agents and chemotherapy · 2025Article
- Not your Mother's MAPKs: Apicomplexan MAPK function in daughter cell budding.PLoS pathogens · 2022Review
- Article
- Two old drugs, NVP-AEW541 and GSK-J4, repurposed against the Toxoplasma gondii RH strain.Parasites & vectors · 2020Article
- Fussing About Fission: Defining Variety Among Mainstream and Exotic Apicomplexan Cell Division Modes.Frontiers in cellular and infection microbiology · 2020Article
- Who Needs a Contractile Actomyosin Ring? The Plethora of Alternative Ways to Divide a Protozoan Parasite.Frontiers in cellular and infection microbiology · 2019Review
- Toxoplasma Calcium-Dependent Protein Kinase 1 Inhibitors: Probing Activity and Resistance Using Cellular Thermal Shift Assays.Antimicrobial agents and chemotherapy · 2018Article
- Drug Resistance inFrontiers in microbiology · 2018Review
- In vitro efficacy of bumped kinase inhibitors against Besnoitia besnoiti tachyzoites.International journal for parasitology · 2017Article
- Extended-spectrum antiprotozoal bumped kinase inhibitors: A review.Experimental parasitology · 2017Review
- Drugs in development for toxoplasmosis: advances, challenges, and current status.Drug design, development and therapy · 2017Review
- A MORN1-associated HAD phosphatase in the basal complex is essential for Toxoplasma gondii daughter budding.Cellular microbiology · 2016Article
- Characterization of a Toxoplasma gondii calcium calmodulin-dependent protein kinase homolog.Parasites & vectors · 2016Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toxoplasma gondii is the causative pathogen for Toxoplasmosis. Bumped kinase inhibitor 1NM-PP1 inhibits the growth of T. gondii by targeting TgCDPK1. However, we recently reported that resistance to 1NM-PP1 can be acquired via a mutation in T. gondii mitogen-activated protein kinase like 1 (TgMAPKL-1). Further characterization of how this TgMAPKL-1 mutation restores the inhibitory effect of 1NM-PP1 would shed further light on the function of TgMAPKL-1 in the parasite life cycle. Therefore, we made parasite clones with TgMAPKL-1 mutated at the gatekeeper residue Ser 191, which is critical for 1NM-PP1 susceptibility. Host cell lysis of RH/ku80(-)/HA-TgMAPKL-1(S191A) was completely inhibited at 250 nM 1NM-PP1, whereas that of RH/ku80(-)/HA-TgMAPKL-1(S191Y) was not. By comparing 1NM-PP1-sensitive (RH/ku80(-)/HA-TgMAPKL-1(S191A)) and -resistant (RH/ku80(-)/HA-TgMAPKL-1(S191Y)) clones, we observed that inhibition of TgMAPKL-1 blocked cell cycle progression after DNA duplication. Morphological analysis revealed that TgMAPKL-1 inhibition caused enlarged parasite cells with many daughter cell scaffolds and imcomplete cytokinesis. We conclude that the mutation in TgMAPKL-1 restored the cell cycle-arresting effect of 1NM-PP1 on T. gondii endodyogeny. Given that endodyogeny is the primary mechanism of cell division for both the tachyzoite and bradyzoite stages of this parasite, TgMAPKL-1 may be a promising target for drug development. Exploration of the signals that regulate TgMAPKL-1 will provide further insights into the unique mode of T. gondii cell division.
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