Generating Resistance/ or Tolerance in Vitro in Laboratory Strains of Plasmodium falciparum Using Sub-therapeutic Doses of Artesunate drug

Andrews Appiagyei, Dr. Michael Ofori, Dr Jonelle Mattiacio, St. John Fisher College, 3690 East Ave, 14618

Malaria is one of the major causes of death in the tropical regions of the world with sub-Saharan African countries being affected the hardest due to drug resistance. Epidemiological studies have used lab strains and field isolates of Plasmodium falciparum to help determine and understand the adverse effects of malaria resistance. The hypothesis was assessing resistance in vitro in lab strain 3D7, Plasmodium falciparum, using subtherapeutic doses of the artesunate drug. Plasmodium falciparum, 3D7 lab strain, were tested in SYBR GREEN artesunate drug assays to determine the sensitivity levels of the parasites to the drug and to determine inhibition concentrations of the parasites. Successful susceptibility and resistance to artesunate concentrations were observed over the 12-day period of cultivation. The IC50 was determined to be 0.00058 ug/ml. Data has shown that artesunate resistance is linked to the K13 propeller gene, and therefore PCR analysis was performed to analyze K13 gene sequence changes. The samples sequenced were analyzed using softwares: Bioedit and Clustal Omega. After analysis of the data from the cultured samples, it was shown that there was no correlation to the mutations usually seen in the K13 propeller gene; C580Y, R539T, and Y493H, when subjected to sub-therapeutic doses of artesunate to the parasite culture. There were no significant changes in the sequence on a nucleotide level that could change the protein produced and therefore did not agree with the hypothesis. This study indicates that sub-therapeutic doses of artesunate used on the Plasmodium falciparum parasite is likely to induce extended resistance over time but would need to be over longer periods of time. Artesunate drug pressure could possibly be used to assess resistance influenced strains of the parasite and aid in understanding the dynamics of gene expression in the parasite to escape drug intervention.

Additional Abstract Information

Presenter: Andrews Appiagyei

Institution: St. John Fisher College

Type: Poster

Subject: Biology

Status: Approved

Time and Location

Session: Poster 3
Date/Time: Mon 4:30pm-5:30pm
Session Number: 3089