ArticleProceedings of the National Academy of Sciences of the United States of America2002
Genetic complementation in apicomplexan parasites.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed.
- ExploringAntimicrobial agents and chemotherapy · 2026Article
- Mycophenolic anilides as broad specificity inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitors.Bioorganic & medicinal chemistry letters · 2020Article
- Genetic ablation of purine salvage inProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Transcriptome analysis of pig intestinal cell monolayers infected with Cryptosporidium parvum asexual stages.Parasites & vectors · 2018Article
- Prokaryotic ancestry and gene fusion of a dual localized peroxiredoxin in malaria parasites.Microbial cell (Graz, Austria) · 2015Article
- A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium.The Lancet. Infectious diseases · 2015Review
- Synthesis, in vitro evaluation and cocrystal structure of 4-oxo-[1]benzopyrano[4,3-c]pyrazole Cryptosporidium parvum inosine 5'-monophosphate dehydrogenase (CpIMPDH) inhibitors.Journal of medicinal chemistry · 2014Article
- Expression of the essential Kinase PfCDPK1 from Plasmodium falciparum in Toxoplasma gondii facilitates the discovery of novel antimalarial drugs.Antimicrobial agents and chemotherapy · 2014Article
- Identification of Cryptosporidium parvum active chemical series by Repurposing the open access malaria box.Antimicrobial agents and chemotherapy · 2014Article
- Validation of IMP dehydrogenase inhibitors in a mouse model of cryptosporidiosis.Antimicrobial agents and chemotherapy · 2014Article
- Optimization of benzoxazole-based inhibitors of Cryptosporidium parvum inosine 5'-monophosphate dehydrogenase.Journal of medicinal chemistry · 2013Article
- Phthalazinone inhibitors of inosine-5'-monophosphate dehydrogenase from Cryptosporidium parvum.Bioorganic & medicinal chemistry letters · 2013Article
- Selective and potent urea inhibitors of cryptosporidium parvum inosine 5'-monophosphate dehydrogenase.Journal of medicinal chemistry · 2012Article
- Bacillus anthracis inosine 5'-monophosphate dehydrogenase in action: the first bacterial series of structures of phosphate ion-, substrate-, and product-bound complexes.Biochemistry · 2012Article
- Structure-activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH.Bioorganic & medicinal chemistry letters · 2012Article
- A genetic screen to isolate Toxoplasma gondii host-cell egress mutants.Journal of visualized experiments : JoVE · 2012Article
- The state of research for AIDS-associated opportunistic infections and the importance of sustaining smaller research communities.Eukaryotic cell · 2012Article
- Overexpression of a cytosolic pyrophosphatase (TgPPase) reveals a regulatory role of PP(i) in glycolysis for Toxoplasma gondii.The Biochemical journal · 2011Article
- An insertional trap for conditional gene expression in Toxoplasma gondii: identification of TAF250 as an essential gene.Molecular and biochemical parasitology · 2011Article
- The antibiotic potential of prokaryotic IMP dehydrogenase inhibitors.Current medicinal chemistry · 2011Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
A robust forward genetic model for Apicomplexa could greatly enhance functional analysis of genes in these important protozoan pathogens. We have developed and successfully tested a genetic complementation strategy based on genomic insertion in Toxoplasma gondii. Adapting recombination cloning to genomic DNA, we show that complementing sequences can be shuttled between parasite genome and bacterial plasmid, providing an efficient tool for the recovery and functional assessment of candidate genes. We show complementation, gene cloning, and biological verification with a mutant parasite lacking hypoxanthine-xanthine-guanine phosphoribosyltransferase and a T. gondii cDNA library. We also explored the utility of this approach to clone genes based on function from other apicomplexan parasites using Toxoplasma as a surrogate. A heterologous library containing Cryptosporidium parvum genomic DNA was generated, and we identified a C. parvum gene coding for inosine 5-monophosphate-dehydrogenase (IMPDH). Interestingly, phylogenetic analysis demonstrates a clear eubacterial origin of this gene and strongly suggests its lateral transfer from epsilon-proteobacteria. The prokaryotic origin of this enzyme might make it a promising target for therapeutics directed against Cryptosporidium.
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