Deletion of Plasmodium falciparum ubc13 increases parasite sensitivity to the mutagen, methyl methanesulfonate and dihydroartemisinin
More about Open Access at the CrickAuthors list
Supawadee Maneekesorn Ellen Knuepfer Judith Green Parichat Prommana Chairat Uthaipibull Somdet Srichairatanakool Anthony HolderAbstract
The inducible Di-Cre system was used to delete the putative ubiquitin-conjugating enzyme 13 gene (ubc13) of Plasmodium falciparum to study its role in ubiquitylation and the functional consequence during the parasite asexual blood stage. Deletion resulted in a significant reduction of parasite growth in vitro, reduced ubiquitylation of the Lys63 residue of ubiquitin attached to protein substrates, and an increased sensitivity of the parasite to both the mutagen, methyl methanesulfonate and the antimalarial drug dihydroartemisinin (DHA), but not chloroquine. The parasite was also sensitive to the UBC13 inhibitor NSC697923. The data suggest that this gene does code for an ubiquitin conjugating enzyme responsible for K63 ubiquitylation, which is important in DNA repair pathways as was previously demonstrated in other organisms. The increased parasite sensitivity to DHA in the absence of ubc13 function indicates that DHA may act primarily through this pathway and that inhibitors of UBC13 may both enhance the efficacy of this antimalarial drug and directly inhibit parasite growth.
Journal details
Journal Scientific Reports
Volume 11
Issue number 1
Pages 21791
Available online
Publication date
Full text links
Publisher website (DOI) 10.1038/s41598-021-01267-6
Europe PubMed Central 34750454
Pubmed 34750454
Keywords
Related topics
Type of publication