Characterization of artemisinin resistance in plasmodium falciparum

• Main Author: Rocamora, Frances Maureen C.
• Other Authors: Zbynek Bozdech
• Format: Theses and Dissertations
• Language: English
• Published: 2017
• Subjects: DRNTU::Science::Biological sciences::Molecular biology
• Online Access: http://hdl.handle.net/10356/72647
• Institution: Nanyang Technological University

Artemisinins are an important class of antimalarials because of their remarkable antimalarial activity and exceptional safety profile. However, the decline in efficacy of artemisinin-based drugs jeopardizes global efforts that aim to control and ultimately eradicate malaria. In order to better understand the Artemisinin resistance phenotype, we developed Artemisinin-resistant parasite lines derived from two isogenic clones (6A and 11C) of the 3D7 strain of Plasmodium falciparum using a selection regimen that mimics how parasites interact with the drug in infected patients. Long term in vitro selection produced two parasite lines that displayed profound stage-specific resistance to artemisinin and its relative compounds. Chemosensitivity and transcriptional profiling of ART-resistant parasites indicate that enhanced adaptive responses against oxidative stress and protein damage are associated with the artemisinin resistance phenotype. Genomic characterization of both parasite lines also identified a spectrum of mutated and copy number-variable genes that could play a role in mediating artemisinin sensitivity. Collectively, this work represents a useful resource for investigating artemisinin response and resistance in P. falciparum.