ArticleThe Journal of infectious diseases2014
Amelioration of Cryptosporidium parvum infection in vitro and in vivo by targeting parasite fatty acyl-coenzyme A synthetases.
Article in The Journal of infectious diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Integrated lipidomic and transcriptomic profiling of the host response in human malaria.Genome biology · 2026Article
- Norditerpene Natural Products from Subterranean Fungi with Anti-Parasitic Activity.Microorganisms · 2025Article
- Targeting translation initiation yields fast-killing therapeutics against the zoonotic parasite Cryptosporidium parvum.PLoS pathogens · 2025Article
- Molecular pathogenesis of Cryptosporidium and advancements in therapeutic interventions.Parasite (Paris, France) · 2025Review
- Identification of potent and orally efficacious phosphodiesterase inhibitors in Cryptosporidium parvum-infected immunocompromised male mice.Nature communications · 2024Article
- Anti-Cryptosporidial Drug-Discovery Challenges and Existing Therapeutic Avenues: A "One-Health" Concern.Life (Basel, Switzerland) · 2024Review
- Potent acyl-CoA synthetase 10 inhibitors kill Plasmodium falciparum by disrupting triglyceride formation.Nature communications · 2023Article
- The Effect of Short-Chain Fatty Acids on Growth ofMicroorganisms · 2022Article
- An update onJournal of parasitic diseases : official organ of the Indian Society for Parasitology · 2022Review
- Biosynthesis of triacsin featuring an N-hydroxytriazene pharmacophore.Nature chemical biology · 2021Article
- Pantothenate and CoA biosynthesis in Apicomplexa and their promise as antiparasitic drug targets.PLoS pathogens · 2021Review
- Bicyclic azetidines kill the diarrheal pathogenScience translational medicine · 2020Article
- Novel Antiparasitic Activity of the Antifungal Lead Occidiofungin.Antimicrobial agents and chemotherapy · 2020Article
- Changes in the Microbiome ofMicroorganisms · 2020Article
- Identification of adaptive inhibitors of Cryptosporidium parvum fatty acyl-coenzyme A synthetase isoforms by virtual screening.Parasitology research · 2019Article
- Long-Chain Acyl-CoA Synthetase is Associated with the Growth ofJournal of fungi (Basel, Switzerland) · 2019Article
- The Action of the Hexokinase Inhibitor 2-deoxy-d-glucose on Cryptosporidium parvum and the Discovery of Activities against the Parasite Hexokinase from Marketed Drugs.The Journal of eukaryotic microbiology · 2019Article
- Article
- Discovery of Novel Anti-cryptosporidial Activities From Natural Products byFrontiers in microbiology · 2019Article
- Molecular and Biochemical Characterization of a Type II Thioesterase From the Zoonotic Protozoan ParasiteFrontiers in cellular and infection microbiology · 2019Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundCryptosporidium is emerging as 1 of the 4 leading diarrheal pathogens in children in developing countries. Its infections in patients with AIDS can be fatal, whereas fully effective treatments are unavailable. The major goal of this study is to explore parasite fatty acyl-coenzyme A synthetase (ACS) as a novel drug target.
methodsA colorimetric assay was developed to evaluate biochemical features and inhibitory kinetics of Cryptosporidium parvum ACSs using recombinant proteins. Anticryptosporidial efficacies of the ACS inhibitor triacsin C were evaluated both in vitro and in vivo.
resultsCryptosporidium ACSs displayed substrate preference toward long-chain fatty acids. The activity of parasite ACSs could be specifically inhibited by triacsin C with the inhibition constant Ki in the nanomolar range. Triacsin C was highly effective against C. parvum growth in vitro (median inhibitory concentration, 136 nmol/L). Most importantly, triacsin C effectively reduced parasite oocyst production up to 88.1% with no apparent toxicity when administered to Cryptosporidium-infected interleukin 12 knockout mice at 8-15 mg/kg/d for 1 week.
conclusionsThe findings of this study not only validated Cryptosporidium ACS (and related acyl-[acyl-carrier-protein]-ligases) as pharmacological targets but also indicate that triacsin C and analogues can be explored as potential new therapeutics against the virtually untreatable cryptosporidial infection in immunocompromised patients.
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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.