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Artemether Exhibits Amoebicidal Activity against Acanthamoeba castellanii through Inhibition of the Serine Biosynthesis Pathway
- Source :
- Antimicrobial agents and chemotherapy. 59(8)
- Publication Year :
- 2014
-
Abstract
- Acanthamoeba sp. parasites are the causative agents of Acanthamoeba keratitis, fatal granulomatous amoebic encephalitis, and cutaneous infections. However, there are currently no effective drugs for these organisms. Here, we evaluated the activity of the antimalarial agent artemether against Acanthamoeba castellanii trophozoites and identified potential targets of this agent through a proteomic approach. Artemether exhibited in vitro amoebicidal activity in a time- and dose-dependent manner and induced ultrastructural modification and cell apoptosis. The iTRAQ quantitative proteomic analysis identified 707 proteins that were differentially expressed after artemether treatment. We focused on phosphoglycerate dehydrogenase and phosphoserine aminotransferase in the serine biosynthesis pathway because of their importance to the growth and proliferation of protozoan and cancer cells. The expression of these proteins in Acanthamoeba was validated using quantitative real-time PCR and Western blotting after artemether treatment. The changes in the expression levels of phosphoserine aminotransferase were consistent with those of phosphoglycerate dehydrogenase. Therefore, the downregulation of phosphoserine aminotransferase may be due to the downregulation of phosphoglycerate dehydrogenase. Furthermore, exogenous serine might antagonize the activity of artemether against Acanthamoeba trophozoites. These results indicate that the serine biosynthesis pathway is important to amoeba survival and that targeting these enzymes would improve the treatment of Acanthamoeba infections. Artemether may be used as a phosphoglycerate dehydrogenase inhibitor to control or block Acanthamoeba infections.
- Subjects :
- Proteomics
Apoptosis
Microbiology
Serine
Antimalarials
parasitic diseases
medicine
Animals
Pharmacology (medical)
Phosphoglycerate dehydrogenase
Artemether
Phosphoserine Aminotransferase
Amebicides
Trophozoites
Granulomatous amoebic encephalitis
Mechanisms of Action: Physiological Effects
Phosphoglycerate Dehydrogenase
Transaminases
Cell Proliferation
Pharmacology
Acanthamoeba castellanii
biology
Amebiasis
biology.organism_classification
medicine.disease
Artemisinins
Acanthamoeba
Biosynthetic Pathways
Infectious Diseases
Acanthamoeba keratitis
Biochemistry
Acanthamoeba Keratitis
Encephalitis
medicine.drug
Subjects
Details
- ISSN :
- 10986596
- Volume :
- 59
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Antimicrobial agents and chemotherapy
- Accession number :
- edsair.doi.dedup.....0e148248047972840190788de6a6d8e7