Protein KIC5 is a novel regulator of artemisinin stress response in the malaria parasite Plasmodium falciparum

Simmons, C. F. et al. (2023) Protein KIC5 is a novel regulator of artemisinin stress response in the malaria parasite Plasmodium falciparum. Scientific Reports, 13, 399. (doi: 10.1038/s41598-023-27417-6) (PMID:36624300) (PMCID:PMC9829687)

Abstract

Artemisinin combination therapies (ACTs) have led to a significant decrease in Plasmodium falciparum malaria mortality. This progress is now threatened by emerging artemisinin resistance (ART-R) linked originally in SE Asia to polymorphisms in the Kelch propeller protein (K13) and more recently to several other seemingly unrelated genetic mutations. To better understand the parasite response to ART, we are characterizing a P. falciparum mutant with altered sensitivity to ART that was created via piggyBac transposon mutagenesis. The transposon inserted near the putative transcription start site of a gene defined as a “Plasmodium-conserved gene of unknown function,” now functionally linked to K13 as the Kelch13 Interacting Candidate 5 protein (KIC5). Phenotype analysis of the KIC5 mutant during intraerythrocytic asexual development identified transcriptional changes associated with DNA stress response and altered mitochondrial metabolism, linking dysregulation of the KIC5 gene to the parasite’s ability to respond to ART exposure. Through characterization of the KIC5 transcriptome, we hypothesize that this gene may be essential under ART exposure to manage gene expression of the wild-type stress response at early ring stage, thereby providing a better understanding of the parasite’s processes that can alter ART sensitivity.

• Item Type: Articles
• Additional Information: This work is supported by NAIID grants R01AI117017 and R01AI130171.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Otto, Professor Thomas

Creator Roles

Otto, T. D.: Supervision

• Authors: Simmons, C. F., Gibbons, J., Zhang, M., Oberstaller, J., Pires, C. V., Casandra, D., Wang, C., Seyfang, A., Otto, T. D., Rayner, J. C., and Adams, J. H.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• Journal Name: Scientific Reports
• Publisher: Nature Research
• ISSN: 2045-2322
• ISSN (Online): 2045-2322
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Scientific Reports 13: 399
• Publisher Policy: Reproduced under a Creative Commons license