ArticleMolecular microbiology2009
Disruption of a mitochondrial MutS DNA repair enzyme homologue confers drug resistance in the parasite Toxoplasma gondii.
Article in Molecular microbiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
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- BONCAT-iTRAQ Labelling Reveals Molecular Markers of Adaptive Responses inPathogens (Basel, Switzerland) · 2024Article
- Early Transcriptional Response to Monensin in Sensitive and Resistant Strains ofFrontiers in microbiology · 2022Article
- A conserved coccidian gene is involved in Toxoplasma sensitivity to the anti-apicomplexan compound, tartrolon E.International journal for parasitology. Drugs and drug resistance · 2020Article
- Evaluating the Antiparasitic Activity of Novel BPZ Derivatives AgainstMicroorganisms · 2020Article
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- Elucidating the mitochondrial proteome ofeLife · 2018Article
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- Toxoplasma gondii-positive human sera recognise intracellular tachyzoites and bradyzoites with diverse patterns of immunoreactivity.International journal for parasitology · 2018Article
- Immune Protection of Rhoptry Protein 21 (ROP21) ofFrontiers in microbiology · 2018Article
- Treatment of Toxoplasmosis and Neosporosis in Farm Ruminants: State of Knowledge and Future Trends.Current topics in medicinal chemistry · 2018Review
- Drug Resistance inFrontiers in microbiology · 2018Review
- Article
- DNA damage regulation and its role in drug-related phenotypes in the malaria parasites.Scientific reports · 2016Article
- Oxidative stress generated during monensin treatment contributes to altered Toxoplasma gondii mitochondrial function.Scientific reports · 2016Article
- Protective immunity against acute toxoplasmosis in BALB/c mice induced by a DNA vaccine encoding Toxoplasma gondii elongation factor 1-alpha.BMC infectious diseases · 2015Article
- Jacobsen catalyst as a cytochrome P450 biomimetic model for the metabolism of monensin A.BioMed research international · 2014Article
- DNA repair mechanisms and Toxoplasma gondii infection.Archives of microbiology · 2014Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
MutS homologues (MSHs) are critical components of the eukaryotic mismatch repair machinery. In addition to repairing mismatched DNA, mismatch repair enzymes are known in higher eukaryotes to directly signal cell cycle arrest and apoptosis in response to DNA-damaging agents. Accordingly, mammalian cells lacking certain MSHs are resistant to chemotherapeutic drugs. Interestingly, we have discovered that the disruption of TgMSH-1, an MSH in the pathogenic parasite, Toxoplasma gondii, confers drug resistance. Through a genetic selection for T. gondii mutants resistant to the antiparasitic drug monensin, we have isolated a strain that is resistant not only to monensin but also to salinomycin and the alkylating agent, methylnitrosourea. We have shown that this phenotype is due to the disruption of TgMSH-1 as the multidrug-resistance phenotype is complemented by a wild-type copy of TgMSH-1 and is recapitulated by a directed disruption of this gene in a wild-type strain. We have also shown that, unlike previously described MSHs involved in signalling, TgMSH-1 localizes to the parasite mitochondrion. These results provide the first example of a mitochondrial MSH that is involved in drug sensitivity and implicate the induction of mitochondrial stress as a mode of action of the widely used drug, monensin.
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